THEORY AND PROBLEMS GENETICS
1- Color blindness in humans is most commonly due to an X-linked recessive
allele. Betty has normal vision, but her mother is color blind. Bill is color
blind. If Bill and Betty marry and have a child together, what is the
probability that the child will be color blind?
2- On average, what proportion of the X-linked genes in the first individual is
the same as that in the second individual?
(a) A male and his mother
(b) A female and her mother
(c) A male and his father
(d) A female and her father
(e) A male and his brother
(f) A female and her sister
(g) A male and his sister
(h) A female and her brother
3- What would the human sexual phenotype (male or female) be?
(a) XX
(b) XY
(c) XO
(d) XXY
(e) XYY
(f) XXYY
(g) XXX
(h) XXXXX
4- Joe has classic hemophilia, which is an X-linked recessive disease. Could
Joe have inherited the gene for this disease from the following persons?
Yes
No
(a) His mother’s mother
____
____
(b) His mother’s father
____
____
(c) His father’s mother
____
____
(d) His father’s father
____
____
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5-Both John and Cathy have normal color vision. After 10 years of marriage
to John, Cathy gave birth to a color-blind daughter. John filed for divorce,
claiming he is not the father of the child. Is John justified in his claim of
nonpaternity? Explain why. If Cathy had given birth to a color-blind son,
would John be justified in claiming nonpaternity?
6- Red–green color blindness in humans is due to an X-linked recessive gene.
A woman whose father is color blind possesses one eye with normal color
vision and one eye with color blindness.
(a) Propose an explanation for this woman’s vision pattern.
(b) Would it be possible for a man to have one eye with normal color vision
and one eye with color blindness?
7- Bob has XXY chromosomes (Klinefelter syndrome) and is color blind. His
mother and father have normal color vision, but his maternal grandfather is
color blind. Assume that Bob’s chromosome abnormality arose from
nondisjunction in meiosis. In which parent and in which meiotic division did
nondisjunction occur? Explain your answer.
8- The Talmud, an ancient book of Jewish civil and religious laws, states that
if a woman bears two sons who die of bleeding after circumcision (removal of
the foreskin from the penis), any additional sons that she has should not be
circumcised. (The bleeding is most likely due to the X-linked disorder
hemophilia.) Furthermore, the Talmud states that the sons of her sisters must
not be circumcised, whereas the sons of her brothers should. Is this religious
law consistent with sound genetic principles? Explain your answer.
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9- How many Barr bodies would you expect to see in human cells containing
the following chromosomes?
(a) XX (d) XXY (g) XYY
(b) XY (e) XXYY (h) XXX
(c) XO (f) XXXY (i) XXXX
10- Red–green color blindness is an X-linked recessive trait in humans.
Polydactyly (extra fingers and toes) is an autosomal dominant trait. Martha
has normal fingers and toes and normal color vision. Her mother is normal in
all respects, but her father is color blind and polydactylous. Bill is color blind
and polydactylous. His mother has normal color vision and normal fingers
and toes. If Bill and Martha marry, what types and proportions of children
can they produce?
11- A color-blind female and a male with normal vision have three sons and
six daughters. All the sons are color blind. Five of the daughters have normal
vision, but one of them is color blind. The color-blind daughter is 16 years old,
is short for her age, and has never undergone puberty. Propose an
explanation for how this girl inherited her color blindness.
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12- A man with a specific unusual genetic trait marries an unaffected woman
and they have four children. Pedigrees of this family are shown in parts a
through e, but the presence or absence of the trait in the children is not
indicated. For each type of inheritance, indicate how many children of each
sex are expected to express the trait by filling in the appropriate circles and
squares. Assume that the trait is rare and fully penetrant.
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For each of the following pedigrees, give the most likely mode of inheritance,
assuming that the trait is rare. Carefully explain your reasoning.
D&A
D&X
Y
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R&X
R&A
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The following pedigree represents the inheritance of a rare disorder in an extended family. What is the most
likely mode of inheritance for this disease? (Assume that the trait is fully penetrant.)
R&X
Classic hemophilia is inherited as an X-linked recessive trait. This pedigree is of hemophilia in the royal families of
Europe
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The Study of Human Genetic Characteristics
Humans are the best and the worst of all organisms for genetic study. On the
one hand, we know more about human anatomy, physiology, and biochemistry
than we know about most other organisms; for many families, we have detailed
records extending back many generations; and the medical implications of genetic
knowledge of humans provide tremendous incentive for genetic studies. On the
other hand, the study of human genetic characteristics presents some major
obstacles.
First, controlled matings are not possible. With other organisms, geneticists
carry out specific crosses to test their hypotheses about inheritance. We have seen,
for example, how the testcross provides a convenient way to determine if an
individual with a dominant trait is homozygous or heterozygous. Unfortunately
(for the geneticist at least), matings between humans are more frequently
determined by romance, family expectations, and—occasionally—accident than
they are by the requirements of the geneticist. Another obstacle is that humans
have a long generation time. Human reproductive age is not normally reached until
10 to 14 years after birth, and most humans do not reproduce until they are 18
years of age or older; thus, generation time in humans is usually about 20 years.
This long generation time means that, even if geneticists could control human
crosses, they would have to wait on average 40 years just to observe the F2
progeny. In contrast, generation time in Drosophila is 2 weeks; in bacteria, it’s a
mere 20 minutes. Finally, human family size is generally small. Observation of
even the simple genetic ratios that we learned in Chapter 3 would require a
substantial number of progeny in each family. When parents produce only 2
children, it’s impossible to detect a 3:1 ratio. Even an extremely large family with
10 to 15 children would not permit the recognition of a dihybrid 9:3:3:1 ratio.
Although these special constraints make genetic studies of humans more complex,
understanding human heredity is tremendously important. So geneticists have been
forced to develop techniques that are uniquely suited to human biology and culture.
Concepts
Although the principles of heredity are the same in humans and other
organisms, the study of human inheritance is constrained by 1) the inability to
control genetic crosses, 2) the long generation time, and 3) the small number
of offspring.
|Page8
Analyzing Pedigrees
An important technique used by geneticists to study human inheritance is the pedigree. A
pedigree is a pictorial representation of a family history, essentially a family tree that outlines
the inheritance of one or more characteristics.
Standard symbols are
used in pedigrees.
|Page9
| P a g e 10
I- Autosomal
a) Recessive Traits
Concepts
1. Autosomal recessive traits appear with equal frequency in males and
females.
2. Affected children are commonly born to unaffected parents, and the trait
tends to skip generations.
3. Recessive traits appear more frequently among the offspring of
consanguine matings.
I-
| P a g e 11
I- Autosomal
b) Dominant Traits
Concepts
1. Autosomal dominant traits appear in both sexes with equal frequency.
2. Affected persons have an affected parent (unless they carry new
mutations), and
3. The trait does not skip generations.
4. Unaffected persons do not transmit the trait.
| P a g e 12
II- X-Linked
a) Recessive Traits
Concepts
1.
2.
3.
4.
Rare X-linked recessive traits appear more often in males than in females
and
Are not passed from father to son.
Affected sons are usually born to unaffected mothers;
Thus X-linked recessive traits tend to skip generations.
| P a g e 13
II- X-Linked
b) Dominant Traits
Concepts
1. X-linked dominant traits affect both males and females.
2. Affected males must have affected mothers (unless they possess a new
mutation), and
3. They pass the trait on to all their daughters.
| P a g e 14
III- Y-Linked Traits
Concepts
1. Y-linked traits appear only in males and
2. Are passed from a father to all his sons.
| P a g e 15
Supplemental Lecture (97/06/10 update) by Stephen T. Abedon (abedon.1@osu.edu)
1. Chapter title: Pedigree Analysis Problems
a. A list of vocabulary words is found toward the end of this document
2. Vocabulary
a. No entry.
3. Practice questions - The below questions are from pp. 60, 68-70 of Sinnott et
al., 1958:
a. Which best describes the genetics of the afflicting allele in the following
pedigree (it is a pedigree of taste blindness)? [PEEK]
i. autosomal dominant
ii. autosomal recessive
iii. X-linked dominant
| P a g e 16
iv.
v.
vi.
X-linked recessive
Y-linked dominant
Y-linked recessive
b. Albinism is inherited as an autosomal recessive. In the figure below,
assuming that persons from the general population are not heterozygous
for albinism (Aa), what are the genotypes of all persons whose genotypes
are known? (i.e., indicate the genotypes on the figure for all
known AA, Aa, and aaindividuals) [PEEK]
| P a g e 17
c. A blue-eyed man marries a brown-eyed woman. They have one child,
who is blue eyed. What are the genotypes of all the individuals
mentioned?[PEEK]
d. Given the below pedigree, would you expect to find more of in
Cleopatra-Berenike III compared with the general population? (figure
from p. 283 of R. Lewis, 1998, Life Third Edition. McGraw Hill,
Boston, Mass.). [PEEK]
i. Loci which are heterozygous
ii. Loci which are homozygous for rare alleles
iii. Loci which display epistasis
iv. Loci which display codominance
v. Alleles
vi. Loci
e. Suppose that an allele, b, of a sex-linked gene is recessive and lethal. A
man marries a woman who is heterozygous for this gene. If this couple
had a large number of normal children, what would be the predicted sex
| P a g e 18
f.
g.
h.
i.
j.
k.
l.
m.
ratio of these children (ratio of male children to female children)?
(adapted from J.L. Gould and W.T. Keeton (1996). Biological
Science. Sixth Edition. W.W. Norton & Company. New York. P.
443) [PEEK]
In Drosophila melanogaster there is a dominant allele for gray body
color and a dominant allele of another gene for normal wings. The
recessive alleles of these two genes result in black body color and
vestigial wings, respectively. Flies homozygous for gray body and
normal wings are crossed with flies that have black bodies and vestigial
wings. The F1 progeny are then crossed, with the following results:
Gray body, normal wings: 236
Black body, vestigial wings: 253
Gray body, vestigial wings: 50
Black body, normal wings: 61
Would you say that these two genes are linked? If so, how many map
units apart are they on the linkage map? (adapted from J.L. Gould and
W.T. Keeton (1996). Biological Science. Sixth Edition. W.W. Norton &
Company. New York. P. 443) [PEEK]
An afflicted woman marries an afflicted man. The allele causing the
affliction is recessive to the wild type allele. What fraction of their
children will be silent carriers? What fraction will be afflicted? [PEEK]
For the following pedigree, how does the afflicting allele impact on
phenotype? (figure is from M.R Cummings (1988). Human Heredity:
Principles and Issues West Publishing Company. New York. p.
113) [PEEK]
i. it displays complete dominance
ii. it is recessive to the non-afflicting allele otherwise found at the
same loci
iii. it displays epistasis
iv. it displays pleiotropic effects
v. it produces a tRNA product
vi. it is a Mendelian ratio
| P a g e 19
p.
q.
r.
4.
n. If a husband and wife have four daughters. Under most circumstances,
what is the probability that their fifth child will also be a girl? (adapted
from G.T. Licata & W.H. Garnsey (1986). A General Review of Biology
2nd Edition. N & N Publishing, Middletown, NY, p. 119 [PEEK]
o. A male cat has short hair, a stubby tail, and extra toes. A female cat has
long hair, a long tail, and extra toes. The genes and alleles are as follows:
L = short hair; l = long hair
M = stubby tail; m = long tail
P = extra toes; p = normal number of toes
s. The two cats have kittens. One kitten has long hair, a long tail, and no
extra toes. Another has short hair, a stubby tail, and extra toes. The third
kitten has short hair, a long tail, and no extra toes. What is the genotype
of the father. (adapted from R. Lewis (1998). Life Third Edition.
McGraw-Hill, Boston, Mass., p. 283)[PEEK]
t. The recombination frequency between linked genes A and B is 40%,
between B and C is 20%, between C and D is 10%, between C and A is
20%, and between D and B is 10%. What is the sequence of the genes on
the chromosome? (adapted from J.L. Gould and W.T. Keeton
(1996). Biological Science. Sixth Edition. W.W. Norton & Company.
New York. P. 443)[PEEK]
Practice question answers
a. ii, autosomal recessive.
b. in the figure below, all individuals from the general population (i.e.,
married in spouses) are AA. All circled individuals are Aa. All afflicted
individuals areaa.
| P a g e 20
c. if b is the recessive blue-eyed allele and B the dominant brown-eyed
allele, then the man is bb, the woman Bb, and the child bb.
d. ii, Loci which are homozygous for rare alleles
e. 1:2 (i.e., half the male children would die)
f. (50 +61) / (236 + 253 + 50 +61) = 18.5, so yes and 18.5 map units apart
g. All will be afflicted and none will be silent carriers.
h. i, it displays complete dominance.
i. 0.5
j. Ll Mm Pp
k. A-C-D-B
5. References
a. Sinnott, E.W., Dunn, L.C., Dobzhansky, T. (1958). Principles of
Genetics. Fifth Edition. McGraw-Hill Book Co., Inc. New York. p. 60,
68-70.
Genetics Vocabulary
| P a g e 21
1.
2.
Allele — alternative forms of a gene for each variation of a trait of an organism
3.
Diploid — cell with two of each kind of chromosome; is said to contain a diploid, or
2n, number of chromosomes
4.
5.
6.
7.
8.
Dominant — observed trait of an organism that mask the recessive form of a trait
Crossing over — exchange of genetic material between non-sister chromatids from
homologous chromosome during prophase I of meiosis; results in new allele
combinations
Egg — haploid female sex cell produced by meiosis
Fertilization — fusion of male and female gametes
Gamete — male and female sex cells, sperm and eggs
Genetic recombination — major source of genetic variation among organisms caused
by re-assortment or crossing over during meiosis
9. Genetics — branch of biology that studies heredity
10.
Genotype — combination of genes in an organism
11. Haploid — cell with one of each kind of chromosome; is said to contain a haploid or
n, number of chromosomes.
12.
13.
14.
Heredity — passing on of characteristics from parents to offspring
15.
16.
Homozygous — when there are two identical alleles for a trait
Heterozygous — when there are two different alleles for a trait
Homologous chromosome — paired chromosomes with genes fro the same
traits arranged in the same order.
trait.
Hybrid — offspring formed by parents having different forms of a specific
17.
Law of independent assortment — Mendelian principal stating that genes for
different traits are inherited independently of each other.
18.
Law of segregation — Mendelian principal explaining that because each plant
has two different alleles, it can produce two different types of gametes. During
fertilization, male and female gametes randomly pair to produce four combinations
of alleles
19.
Meiosis — type of cell division where one body cell produces for gametes,
each containing half the number of chromosomes in a parent’s body.
20.
Nondisjunction — failure of homologous chromosomes to separate properly
during meiosis; results in gametes with too many or too few chromosomes
21.
22.
23.
Phenotype — outward appearance of an organism, regardless of its genes.
Pollination — transfer of male pollen grains to the pistil of a flower
Recessive — trait of an organism that can be masked by the dominant form
of a trait
| P a g e 22
24.
Sexual reproduction — pattern of reproduction that involves the production
of subsequent fusion of haploid cells.
25.
26.
27.
Sperm — haploid male sex cells produced by meiosis
Trait — characteristic that is inherited; can be either dominant or recessive
Zygote — diploid cell formed when a sperm fertilizes an egg.
Terms to know in Mendelian Genetics
alleles
The different forms of a gene. Y and y are different alleles of the gene that
determines seed color. Alleles occupy the same locus, or position, on
chromosomes.
autosomal
A locus on any chromosome but a sex chromosome. Not sex-linked.
co-dominant alleles
Two different alleles at a locus are responsible for different phenotypes, and
both alleles affect the phenotype of the heterozygote. For example, consider the
situation where there are three alleles A,B, and O that determine human blood
type. Three possible genotypes are AA, BB, OO that correspond to the
phenotypes of blood type A, B, and O respectively; Two other genotypes are
AO and BO that correspond to blood types A and B, respectively because the O
allele is recessive, The remaining genotype is AB, corresponding to blood type
AB. Both the A and B alleles contribute to the phenotype of the heterozygote.
Thus the alleles A and B are said to be co-dominant.
complete linkage.
Complete linkage describes the inheritance patterns for 2 genes on the same
chromosome when the observed frequency for crossover between the loci is
zero.
dioecious
Organisms produce only one type of gamete; i.e. humans
dominant trait.
A trait expressed preferentially over another trait.
Drosophila melanogaster
The fruit fly, a favorite organism for genetic analysis.
epistasis.
One gene masks the expression of a different gene for a different trait.
F1 generation
| P a g e 23
Offspring of a cross between true breeding plants, homozygous for the trait of
interest
F2 generation
Offspring of a cross involving the F1 generation.
genotype
The genetic constitution of an organism with respect to a trait. For a single trait
on an autosome, an individual can be homozygous for the dominant trait,
heterozygous, or homozygous for the recessive trait. Yellow seeds are
dominant, but yellow seeded plants could have a genotype of either YY or Yy.
hemizygous
If there is only one copy of a gene for a particular trait In a diploid organism,
the organism is hemizygous for the trait, and will display a recessive
phenotype. X-linked genes in fly or human males are hemizygous.
heterozygous
Differing alleles for a trait in an individual, such as Yy.
homologous chromosomes
The pair of chromosomes in a diploid individual that have the same overall
genetic content. One member of each homologous pair of chromosomes in
inherited from each parent.
homozygous
Both alleles for a trait are the same in an individual. They can be homozygous
dominant (YY), or homozygous recessive (yy).
hybrid
heterozygous; usually referring to the offspring of two true-breeding
(homozygous) individuals differing in the traits of interest.
incomplete dominance
Intermediate phenotype in F1, parental phenotypes reappear in F2. The flowers
of the snapdragon plant can be red, pink, or white. Color is determined at a
single locus. The genotype RR results in red flowers and rr results in white
flowers. The heterozygote genotype of Rr results in pink flowers. When the
heterozygote has a different, intermediate phenotype compared to the
homozygous dominant or homozygous recessive individuals, this is said to be
incomplete dominance.
lethal alleles.
Mutated genes that are capable of causing death.
linkage.
genes that are inherited together on the same chromosome. Three inheritance
patterns are possible: non-linkage, Partial linkage, and complete linkage.
mendel's law of independent assortment of alleles.
Alleles of different genes are assorted independently of one another during the
formation of gametes.
| P a g e 24
mendel's law of segregation
Alleles segregate from one another during the formation of gametes.
monoecious
Organisms produce both male and female gametes; i.e. garden pea.
monohybrid cross.
Cross involving parents differing in only one trait.
mutation
Change in the DNA sequence of a gene to some new, heritable form. Generally,
but now always a recessive allele.
non-linkage.
Non-linkage describes the inheritance patterns for 2 genes on the same
chromosome, when the expected frequency for crossover between the loci is at
least one. The observed inheritance patters for non-linked genes on the same
chromosome is the same as for 2 genes on different chromosomes.
partial linkage.
Partial linkage describes one of the inheritance patterns for 2 genes on the same
chromosome, when the expected frequency for crossover between the loci is
greater than zero but less than one. From partial linkage analysis we can learn
about the order and spacing of genes on the same chromosome.
phenotype
The physical appearance of an organism with respect to a trait, i.e. yellow (Y)
or green (y) seeds in garden peas. The dominant trait is normally represented
with a capital letter, and the recessive trait with the same lower case letter.
pleiotropic.
A single gene determines more than one phenotype for an organism.
recessive trait.
The opposite of dominant. A trait that is preferentially masked.
reciprocal cross
Using male and female gametes for two different traits, alternating the source
of gametes.
sex chromosomes
Sex determination is based on sex chromosomes
sex-linked.
A gene coded on a sex chromosome, such as the X-chromosome linked genes
of flies and man.
test cross
Generally a cross involving a homozygous recessive individual. When a single
trait is being studies, a test cross is a cross between an individual with the
dominant phenotype but of unknown genotype (homozygous or heterozygous)
with a homozygous recessive individual. If the unknown is heterozygous, then
approximately 50% of the offspring should display the recessive phenotype.
| P a g e 25
true-breeding
Homozygous for the true-breeding trait.
wild-type allele
The non-mutant form of a gene, encoding the normal genetic function.
Generally, but not always a dominant allele.
The Biology Project
University of Arizona
Tuesday, August 13, 1996
denicew@u.arizona.edu
http://www.biology.arizona.edu
All contents copyright © 1996. All rights reserved.
Glossary of terms used in molecular
genetics
Acceptor site - see splice acceptor site
Acentric fragment A piece of chromosome without a centromere
3' UTR, 3' Untranslated Region The part of the mRNA which lies between the
signal for the termination of translation (the stop codon) and the polyA tail.
5' UTR, 5' Untranslated Region The part of the mRNA which comes before the
AUG codon which initiates translation.
Acrocentric A chromosome with its centromere very close to (but not actually at) one
end. It applies to human chromosomes 13, 14, 15, 21 and 22.
Allele One of alternative forms of a gene at a particular locus.
Alu repeat sequence A member of a family of repeated DNA sequence elements
which is particularly abundant in the primates (about 3 × 105 copies in the human
genome). Alus are approximately 300 base pairs long, often contain a site for
the restriction endonuclease Alu I and have been derived from a small number of
active members via transcription and retroposition (which still continues). The
insertion of an alu element can cause mutation.
| P a g e 26
Amino Acid One of the building blocks of proteins. See your textbooks!
Amniocentesis A procedure used in antenatal diagnosis of genetic abnormality in
which a sample of the amniotic fluid surrounding the foetus is removed, and either
DNA is prepared directly from the amniocytes suspended in it or these cells may be
cultured and their chromosomes examined.
Amniocyte A foetal cell found suspended within the amniotic fluid surrounding the
foetus.
Amplification



As in PCR Amplification - exponential increase of the number of copies of a
specific DNA sequence in vitro by using the polymerase chain reaction.
As in various types of gene mutation such as trinucleotide repeat amplification
or myc gene amplification - naturally occuring aberrations which have greatly
increased the copy number of a triplet repeat or of a whole gene respectively in
vivo.
As in amplified library, a clone library which has undergone at least one round
of colony or plaque formation followed by resuspension.
Anaphase The stage in a cell division at which the chromosomes move to opposite
ends of the spindle
Aneuploid A set of chromosomes which does not contain an exact multiple
of haploid sets of chromosomes.
Anticipation The process whereby some genetic diseases get more severe in each
successive generation.
Antisense strand (of DNA) The DNA strand which carries
the complementary sequence to the mRNA. It is of course the strand which is
actually transcribed into the mRNA.
Archaebacteria A phylum of organisims distinct from both prokaryotes and
eukaryotes.
Ascertainment The method by which individuals (and families) come to attention for
genetic study.
| P a g e 27
Assortative mating The tendency for mates to be chosen non randomly. Mates may
be chosen for a shared characteristic (positive assortative mating) or chosen to be
different (negative ditto)
Assortment The movement of homologous chromosomes to opposite poles in the
first meiotic division (and chromatids in the second meiotic division) leading to the
segregation of alleles. It is (usually) random with respect to each chromosome.
Autosome A chromosome which is not a sex chromosome.
Autoradiography A technique which reveals the position of radioactive isotope (such
as 35S, 32P or 33P) within an experimental result. The experiment containing a
radioactive label is held tightly against a piece of unexposed X-ray film in the dark.
After an appropriate period the X-ray film is developed and the positions on the film
which have been exposed to radiation from the isotope are revealed.
Bacteriophage A virus which infects bacteria. Modified bacteriophages are used
as cloning vectors. Two which are commonly encountered are bacteriophage lambda
and bacteriophage M13.
Banding A reproducible pattern of light and dark staining along the length of a
chromosome.
Barr body An X chromosome which is condensed and inactive and which shows as a
dark staining blob in an interphase nucleus.
Base A (chemically) basic part of a nucleic acid. Adenine (A), thymine (T), cytosine
(C), guanine (G) and uracil (U). See base pair, nucleoside and nucleotide.
Base pair (bp) The fundamental unit of a double stranded DNA molecule, (more
strictly - a nucleotide pair). The base Adenine on one strand is paired with Thymine
on the other and Guanine with Cytosine. The lengths of double stranded DNA
molecules are frequently given in bp (or nucleotide pairs).
Bivalent A pair of homologous chromosomes closely associated
in prophase and metaphase of the first meiotic division.
Blot To transfer DNA, RNA or Protein from an electrophoresis medium (such as
agarose or polyacrylamide) to a support (such as a nylon membrane) where it
becomes accessible for analysis (by hybridisation to a nucleic acid probe, or by
binding a specific antibody). See Southern, Northern and Western blots.
| P a g e 28
Candidate gene A gene which by virtue of either its function or of its map position
might be considered as the possible cause of a genetic disease when mutant.
Carrier A person heterozygous for a recessive trait.
cDNA - Complementary DNA - DNA which has at some point in its history been
made by copying RNA using the enzyme reverse transcriptase. See theTechniques
lecture
CentiMorgan (cM) The unit of distance in genetic maps. Over short distances, if two
genes are 1 cM apart then they will recombine on average 1% of the time.
Centromere The point at which a chromosome attaches to the spindle fibres during
cell division. Visible as a constriction in the thickness of a metaphasechromosome.
Chain termination mutation A mutation which leads to the premature termination of
the polypeptide chain specified by the mutant gene. Nonsense mutations,frameshift
mutations and splice junction mutations can all give rise to premature chain
termination.
Chiasma (plural chiasmata) Literally a cross. The point at which a genetic
recombination event has occurred, visible as a cross-over in meiotic prophase.
Chimaera (chimera) An animal (or plant) made up from a mixture of cells from
more than one species. Also (in human genetics), an individual made up from cells
derived from two or more zygotes.
Chorionic villus sampling (CVS) A technique used in antenatal diagnosis where a
small amount of placental tissue is removed at about 8 - 9 weeks of gestation by
transcervical aspiration. Foetal DNA or chromosomes can then be prepared from the
tissue. See also amniocentesis
Chromatid A chromosome at metaphase can be seen to be made up of two identical
sister chromatids held together at the centromere. At anaphase one chromatid will go
to each pole.
Chromatin The complex of DNA in the nucleus with histone and non-histone
proteins.
Chromosome The structure which is built up around each nuclear DNA molecule. It
is comprised of a single (double stranded) DNA molecule with
associatedhistone proteins, non-histone proteins and RNA. It is most easily viewed at
| P a g e 29
its most condensed (at metaphase of mitosis) when its structure has been duplicated to
give two chromatids. All normal human chromosomes have a centromere, two arms
and two telomeres.
Chromosome jumping A (difficult?) cloning method which can be used to isolate
clones at a desired distance (in the range of 100 - 300 kb) along a chromosome from
the starting clone.
Chromosome walking A method of making a detailed map of a chromosome by
isolating successive overlapping clones. Usually each clone is used as a probe to
isolate the next.
Clone


noun Is frequently used to mean a DNA molecule which has been replicated in
a micro-organism such as a bacterium or yeast to make many thousands or
millions of identical molecules. It also means an individual who is genetically
identical to another individual. This might mean an identical twin but it is often
used to mean a cell line in which each cell is identical to all the others because
they are all derived by cell division from a common ancestor.
Verb to carry out the process of replicating an individual or a specific DNA
molecule.
Coding strand Within a gene, this is the DNA strand which has the same sequence of
bases as the primary transcript (with the substitution of T for U obviously). It is also
called the sense strand.
Coding sequence That part of a gene which contains the codons which will, via
a mRNA intermediate, be translated into polypeptide. Its antithesis is non-coding
sequence.
Codominant Used to describe alleles which can both be recognised in
the phenotype of a compound heterozygote.
Codon A group of three consecutive nucleotides in mRNA which specifies an amino
acid to be incorporated in the polypeptide product of the gene. See genetic code.
Coefficient of inbreeding The proportion of the genes of an individual in which both
copies are identical by descent from a common ancestor. Alternatively, the chance
that both alleles of any one gene are identical by descent.
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ColonyThe small heap of bacteria which are the descendents of a single bacterium
placed on a nutrient agar dish and allowed to incubate for some hours (usually
overnight).
Colony Screen. Bacterial colonies are grown on a nylon filter placed on nutrient agar.
The colonies are lysed in situ in conditions similar to those of a Southern blotso that
the DNA which each contains adhers to the filter at the site of each colony and is
available for hybrisation to a specific probe. In this way a clone which contains the
probe sequence may be identified.
Complementary (As in complementary strand) having the sequence of nucleotides
which will form a base paired double helix with another strand of DNA or RNA.
Complementary DNA see cDNA
Complementation The ability of two different mutations to produce a wild
type phenotype in a double heterozygote. This gives a very strong indication that they
do not both affect the same gene (cases of intragenic complementation are very rare).
Compound heterozygote An individual in whom both alleles at a single locus carry a
different mutation.
Complexity In molecular genetics, used to describe a DNA molecule or a mixture of
DNA molecules. It is the length of the sequence without including any sequence
repetition.
Congenital Present at birth but not necessarily inherited.
Consanguineous mating A mating in which male and female are related by descent.
Contiguous gene syndrome A syndrome caused by a deletion which has removed
one copy of a number of genes which are close together in the genome.
Cosmid A type of cloning vector which is based on a plasmid but which contains one
copy (or sometimes two copies) of the lambda cohesive end. This enables
recombinant molecules to be packaged into lambda phage particles which are able to
infect recipient bacteria. It is thus a very efficient way of creating libraries of
relatively high molecular weight genomic DNA. The average insert size in a cosmid is
40 - 45 kb.
C0t 1 DNA Eukaryotic DNA which has been denatured and allowed to reanneal to a
C0t value of 1. The double stranded component is then purified from the single
| P a g e 31
stranded component and is supplied commercially. It contains most of the repetitive
component of the genome but very little single copy DNA.
CpG means the dinucleotide: Cytidine joined by a 5´ to 3´ phospho-diester linkage to
Guanidine as part of a normal DNA strand.
Crossover The reciprocal exchange of genetic material between homologous
chromosomes in meiosis. A point along the length of a meiotic bivalent where the
homologous chromosomes can be seen to have exchanged chromatids.
See chiasma and genetic recombination.
Cryptic splice site A DNA sequence which is similar to the consensus sequence of
a splice site but which is not normally used. It may be activated if a mutationalters or
removes a genuine nearby site. It may be in coding or non-coding DNA sequence.
Cytogenetic location The region (or point) in the cytogenetic banding pattern within
(or at) which a gene (or cloned DNA fragment etc.) is thought to lie. A cytogenetic
map is comprised of many such pieces of information.
Deletion A mutation resulting in the loss of normal DNA sequence. A deletion may
be of any size from 1 nucleotide pair to the loss of most of a chromosome.
Denaturation - of DNA - conversion from double stranded to single stranded form,
often by heating sometimes by treatment with alkali. - of protein - treatment which
destroys the tertiary structure of a protein.
Deoxyribonucleic acid see DNA
Depth as in "depth of library". The average number of times any sequence, originally
present in a single copy in the genome, will be represented in a genomic library. A
typical library will have a depth of from 3 to 10.
Dicentric a structurally abnormal chromosome with two centromeres
Diploid having two haploid sets of chromosomes
Dizygotic twins twins arising by the fertilisation of two eggs by two sperm. therefore
no more identical than normal sibs.
DNA The molecule in which the genetic information of most organisms is encoded.
See textbooks and first year lecture notes for more detail!
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DNA fingerprinting A process by which an individual can be uniquely identified
(well, narrowed down substantially!) by testing for multiple DNA polymorphisms.
Often, for forensic purposes, the source of the DNA may be only a tiny spot of blood
or a hair root etc. See here for a diagram
DNA methylation in vertebrates The addition of a methyl group to a cytosine base of
a CpG dinucleotide to form 5-methylcytosine. in micro-organisms many other
methylation positions may be used.
DNA polymerase an enzyme which makes DNA from nucleotide triphosphates.
Usually it requires a single stranded template (either DNA or RNA) and a short primer
(again either DNA or RNA) to enable it to make a complementary copy.
Dominant An allele is dominant if its effect can be observed in the phenotype of
a heterozygote.
Dominant negative mutation The mutant polypeptide disrupts the function of the
wild type polypeptide in heterozygotes.
Donor site see splice donor site.
Dosage compensation The imbalance caused by having two copies of the X
chromosome in females compared to only one copy in males is countered (in humans)
by X inactivation or (in Drosophila) by reducing the relative level of activity of X
linked genes in females.
Downstream Genes have an orientation which is defined by their direction of
transcription (5' to 3'). Downstream means further in the direction of transcription of a
gene and even possibly beyond its end.(Opposite is upstream.)
Electrophoresis A technique whereby molecules are separated by movement in an
electric field. In zone electrophoresis the molecules are ordered on the basis of their
charge to weight ratios. In agarose and polyacrylamide gel electrophoresis the matrix
plays a significant role in sieving the molecules which are therefore separated much
more on the basis of their sizes.
Enhancer A DNA sequence, usually, but not necessarily, near the promoter, which
will increase the level of transcription of genes attached to it on the same DNA
molecule. Its effect is independent of orientation and though it is usually within
5 kb of a gene, it may be able to work over distances as great as 50 kb. It may
beupstream or downstream of the gene.
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Epigenetic any factor which influences the phenotype which is not part of
the genotype.
EST, Expressed sequence tag An (usually) incompletely sequenced cDNA.
Knowledge of sequence allows the design of a PCR reaction which may be used to
test for its presence. Most ESTs have been generated from the 3' UTRs of genes.
Euchromatin noun (and Euchromatic adjective) chromatin with a normal pattern of
replication and gene expression. Compare with heterochromatin.
Eukaryote A class of organisms (which may be single or multicellular) in which the
genetic material is contained within a nucleus. There are other specialised structures
too which are unique to eukaryotes. See prokaryotes and archaebacteria.
Euploid A genome which contains a whole number of haploid sets of chromosomes.
See aneuploid.
Exon One of the parts of a gene whose sequence is present in the mature mRNA.
Expressivity The degree of expression of a mutant phenotype. If there is a variable
expressivity it may range from mild symptoms to a severe phenotype. See
alsopenetrance.
Familial trait A trait which is more common in the relatives of an affected person.
Fitness A measure of an organism’s or a genotype’s ability to leave offspring in the
next generation. It is the number of offspring left by that individual (or the average
left by individuals of a particular genotype) divided by the average number of
offspring left by all members of the population.
Flanking sequence The DNA on either side of a gene. See upstream and downstream.
Founder effect A high frequency of a particular allele in a population caused by it
having been present in one or more members of a small number of individuals from
whom the population is descended.
Frameshift mutation A mutation which, by deletion or addition of a number
of basepairs which is not divisible by three, causes an alteration in the reading
frame of a gene.
G bands The pattern of dark and light coloured Giemsa stained bands on metaphase
chromosomes. See Giemsa banding
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g force The force exerted on an object due to gravity. The centrifugal force exerted by
a centrifuge is often given in units of G. Where G = the force exerted on a 1kg mass at
the Earth's surface.
Gamete A sperm or an ovum.
Gene In Mendelian terms - a unit of inheritance. In molecular terms - a region of
DNA which contains the information to create either a functional RNA or a
polypeptide chain.
Gene dosage The number of copies of a gene which are present in the genome.
Gene family A number of genes which resemble each other in DNA sequence,
presumably because they have evolved by gene duplication and subsequent
divergence.
Gene flow The movement of alleles from one population into another.
Gene map A diagram of the relative positions of genes within the genome
Gene pool All the alleles at a particular locus present in a population.
Genetic code The rules for converting the sequence of nucleotides in mRNA into a
sequence of amino acids in a polypeptide.
Genetic disease A disorder, which may or may not be apparent at birth, which is a
consequence of a mutation present in one or more of the patient's genes.
Genetic Drift Random changes in allele frequencies from one generation to another
in finite (small) populations
Genetic heterogeneity Similar phenotypes caused by mutations in more than
one gene.
Genetic map A map showing the distances between markers in terms of the
frequency of genetic recombination between them.
Genetic marker A polymorphic locus which can be used in linkage studies. The
polymorphism may be anything to do with the DNA at the locus or its possible
product so long as it can be recognised with an appropriate test. Examples include
polymorphisms such as a single nucleotide change, an RFLP,
a microsatellitepolymorphism, an electrophoretic variant of a protein, a blood group,
a genetic disease etc.
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Genome The complete DNA sequence of an organism (though it may sometimes be
used in the sense of ‘mitochondrial genome’ or ‘nuclear genome’).
Genomic DNA DNA derived from the genome, as distinct to cDNA. It may have
been directly purified but it may also have been manipulated in some way, byPCR for
instance or by cloning.
Genotype The alleles present in an individual at the locus (loci) under consideration.
Alternatively, the sum of all the alleles present in a genome.
Germline The cells which are in direct mitotic line of descent from the zygote to
its gametes. As distinct from somatic cells.
Germline mosaicism Two populations of cells making up the germline of one
individual. Caused by mutation and proliferation of one cell out of the population of
germline cells.
Giemsa banding A way of treating metaphase chromosomes with trypsin and Giemsa
stain to give a reproducible pattern of dark and light coloured bands.
Haploid In the human case, having exactly one copy of each of the autosomes and
one sex chromosome. (In the case of an organism with a non-chromosomal method of
sex determination then having just one copy of the genome.)
Haplotype A set of closely linked alleles which are inherited together.
Hardy-Weinberg law A rule which relates the frequencies of genotypes at a locus in
a population to the frequencies of the alleles at that locus.
Hemizygous Having only one copy of a chromosome rather than the usual two. Used
most often in describing the X chromosome in males but can be used to describe any
chromosome or (in the case of a deletion) any segment of chromosome.
Heritability The extent to which a trait is genetically determined.
Heterochromatin Chromatin which is condensed in interphase and which replicates
later than the rest of the genome. Can be subdivided into facultativeheterochromatin
(which describes the inactivated X chromosome, inactivated randomly in only half the
cells of a female) and constitutive heterochromatin which contains a high content
of tandemly repeated (satellite) DNA sequences and relatively few genes and which is
always heterochromatic.
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Heterokaryon A cell with more than one nucleus formed by the fusion of two or
more cells (usually of different species). The first stage in making a somatic cell
hybrid.
Heteromorphism Normal variation in the shape or staining of a chromosome. It may
often involve variation in the amount of heterochromatin.
Heterozygote (adj. heterozygous) An individual having two different alleles at
a locus.
Histones Very basic proteins which bind tightly to the acidic DNA to form a
nucleosome - the basic building block of chromatin. They are highly conserved
throughout eukaryotic evolution.
Homologous chromosomes A pair of chromosomes containing essentially the same
genetic information which have been inherited one from each parent.
Homozygote (adj. homozygous) An individual having two identical alleles at a locus.
Housekeeping gene A gene which is expressed at a similar level in almost all cells,
presumably because its product is required for cell viability.
Hybrid An organism made by crossing two different species. (Or, of a cell line, a cell
line made by fusing cells of two different species; or of a DNA duplex, having one
strand from one source and one from another.)
Hybridisation Used in molecular biology to describe the process of annealing one
strand of a polynucleotide (DNA or RNA), the probe, to a strand
ofcomplementary sequence (again either DNA or RNA), the target. Also, the process
of forming a hybrid. Used in many techniques such
as Southern and NorthernBlotting, in situ Hybridisation, colony screening.
Imprinting The differential expression of genes depending on whether they were
inherited maternally or paternally.
Inborn error of metabolism A mutation which results in the absence of an enzyme
leading to a metabolic consequence which may be fatal.
Inbreeding The mating of related individuals.
Insertion mutation A mutation caused by the addition of genetic material into a gene.
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In situ hybridisation Hybridisation of a labelled probe to its target which has been
fixed for visualisation by microscopy. It is used to reveal the position of sequences
corresponding to the probe on metaphase chromosomes, in interphase nuclei, on
stretched DNA molecules and also to reveal the cellular location of RNAtranscripts
corresponding to the probe sequence.
Interphase That portion of the cell cycle when the nuclear membranes have formed,
the chromosomes have decondensed and the cell is going about its normal business.
During this interval DNA replication takes place.
Interspersed repetitive DNA DNA sequences which are present many thousands of
times in each haploid genome, which are widely scattered throughout the genome and
which are not particularly concentrated at any point. Examples
include Alu and Line sequences.
Intervening sequence See intron
Intron A part of the gene which is transcribed but which is removed (by the process
of splicing) from the primary transcript in the formation of mRNA. Intronstherefore
remain in the nucleus.
Inversion A chromosomal rearrangement in which a segment of chromosome is
turned end for end. A pericentric inversion includes the centromere, a paracentric
inversion does not.
Isochromosome A chromosome in which one arm has been lost and has been
replaced by a duplicate of the other arm. e.g. iso Xq is a chromosome with two X long
arms and no X short arms.
Isoelectric focussing A technique for separating proteins on the basis of their charge.
The mixture of proteins is placed in a gradient of pH across which an electric field is
applied. The proteins migrate until they reach the point in the gradient at which they
carry no net charge, their isoelectric point.
Isoform Multiple molecular forms of a given protein (or iso enzymes or isozymes if
they are enzymes). Isoforms can usually be separated by electrophoresis or some other
separation technique. They exist because of multiple gene loci or multiple alleles (also
called allelomorphs / allelozymes or allozymes) or subunit interaction or secondary
changes - such as post-translational modification.
Karyotype The chromosomal constitution of an individual.
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kb (kilobase) 1000 nucleotides or nucleotide pairs - a unit of single or double
stranded nucleic acid length measurement.
Kindred A very extended pedigree.
Kinetochore The part of the centromere to which the spindle fibres are attached.
Label A chemical tag attached to or included within a molecule to enable its
subsequent identification. Nucleic acids are conveniently labelled by incorporating
radioactive isotopes of phosphorous (32P or 33P) into their sugar phosphate backbones,
proteins may be labelled by incorporating a radioactive isotope of sulphur (35S)into
methionine residues. Alternatively, fluorescent molecules may be attached via side
chains to either nucleotides or to amino acids.
Library A large bank of clones (which may be either genomic or cDNA). The depth
of a genomic library is the number of times which any single copy sequence can be
expected to be recovered from it.
Line element A dispersed repeat family with tens of thousands of copies, each from 1
to 6 kb long. New elements are generated by retroposition of a transcribed copy.
Linkage The tendency of genes close together on the same chromosome to be
inherited together. It can be quantified and used as a mapping tool.
Linkage disequilibrium The occurrence, on the same chromosome, of some
combinations of alleles of closely linked genes more often than would be predicted by
chance.
Linkage map A map of a chromosome showing distances between loci in terms of
the genetic recombination distances between them. See genetic map
Locus Literally, a place. A point on a chromosome or in a genome at which a
specific gene or other marker is found. Often taken (wrongly) to mean gene.
Locus heterogeneity see genetic heterogeneity
Lod Score A statistic giving the level of confidence in an estimate of linkage
distance between two loci.
Lyonisation See X inactivation.
Map position The point at which a marker is found on a genetic map, or at which
a clone is found on a cytogenetic map.
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Meiosis The sequence of two cell divisions which turns a diploid germ cell into
a haploid gamete.
Messenger RNA (mRNA) RNA which leaves the nucleus carrying information
which, by translation, will direct the synthesis of polypeptides.
Metaphase The stage of mitosis (or meiosis) at which the chromosomes are at their
most condensed and at which they are lined up in the centre of the spindle, about to
divide.
Micro array A large number of objects immobilised in a rectangular array on a
microscope slide. The objects may be oligonucleotides, DNA from cDNA clones or
fragments of genomic DNA. The array can be hybridised with a mixture of
two probes labelled in contrasting ways. The ratio of the amounts of each probe which
bind to each target on the array is quantified.
Microsatellite A DNA sequence of from 2 to 6 nucleotides which are tandemly
repeated from about 5 to 5,000 times (usual range 20 - 50 repeats). A locus containing
a microsatellite is often polymorphic because of variation in the repeat number.
Minisatellite A DNA sequence of about 20 to 50 nucleotides which are tandemly
repeated from about 5 to 100 times. A locus containing a minisatellite is
oftenpolymorphic because of variation in the repeat number.
Missense mutation A mutation which changes the amino acid incorporated into the
coded polypeptide chain.
Mitochondrial DNA The DNA of the mitochondrial genome.
Mitochondrial inheritance Inheritance of a character encoded in the mitochondrial
genome.
Mitosis A normal cell division resulting in two genetically identical daughter cells.
Monosomy having only one copy of one of the chromosomes.
Monozygotic twins Two individuals derived from a single fertilised egg and therefore
genetically identical.
Mosaic An individual composed of more than one genetically distinguishable cell
population derived from a single zygote. Not the same as a chimaera.
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Multifactorial inheritance The occurrence of a phenotype as a result of the action of
more than one gene and / or of environmental factors.
Mutagen A physical or chemical factor which increases the mutation rate.
Mutant phenotype A phenotype which is different from the wild type phenotype and
which is caused by the possession of one or more mutant alleles.
Mutation A change in DNA sequence from one generation (or cell generation) to the
next.
Mutation Rate The frequency with which mutations occur.
Nondisjunction The failure of a chromosome pair to separate at the first meiotic
division, or for two chromatids of a replicated chromosome to separate at mitosis(or at
the second meiotic division), so that both pass to the same daughter cell.
Nonhomologous chromosomes Chromosomes which are not homologues...
See Homologous chromosomes.
Nonsense mutation A point mutation which alters a codon so that instead of coding
for an amino-acid it codes for a translation stop signal.
Northern Blot A procedure for measuring the approximate size and abundance of a
specific transcript in a complex mixture of transcripts. Named by (humorous?)
analogy with Southern blot which it greatly resembles. An RNA population is
separated according to size by electrophoresis in an agarose gel, the RNA is
transferred to a nylon membrane by blotting and individual RNA species can be
identified by hybridisation to a radiolabelled DNA probe and autoradiography.
Nucleosome The basic structural unit of chromatin made up of almost two turns of
DNA (146bp) wound around a histone core containing two molecules each of histones
H2A, H2B, H3 and H4.
Nucleoside A nucleotide without the phosphate.
Nucleotide A building block of a nucleic acid consisting of a base (adenine, thymine,
cytosine, guanine, uracil) joined to a sugar (ribose or deoxyribose) and a phosphate.
Null mutation A mutation which leads to the absence of a gene product.
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obligate heterozygote, obligate carrier An individual who is proved on the basis
of pedigree information to carry one copy of a recessive allele even though it cannot
be seen in his or her phenotype.
Oligonucleotide A short (2 - 50 nucleotides) sequence of (usually single stranded)
DNA which has been chemically synthesised for a specific experimental purpose.
Oncogene A dominant gene whose expression leads to uncontrolled cellular
proliferation.
Open reading frame see reading frame
p in cytogenetics, the short arm of a chromosome, in biochemistry, protein as in p16 (a
16 kilodalton protein), in population genetics often used for the frequency of the most
common of the possible alleles at a locus. (see q)
palindrome a double stranded DNA sequence in which the sequence of one strand in
the 5´ to 3´ direction is the same as the sequence of the (oppositely
orientated)complementary strand in the 5´ to 3´ direction.
PCR see polymerase chain reaction
Pedigree The members of a family, also used to describe a diagram of their
relationships one to another and with information on the inheritance of one or more
conditions or genetic loci.
Penetrance The frequency with which individuals with the
necessary genotype express symptoms of a genetic condition.
Phenocopy An individual in whom a phenotype, normally associated with a mutant
gene, has been brought about by some factor in the environment.
Phenotype An individual’s outward appearance (c.f. genotype). It is also used to
incluse to describe a cellular or molecular characteristic, e.g. Blood group A andRFLP
Plasmid A short circular DNA sequence which is replicated within a host bacterium
(or yeast) and which usually confers a selective advantage (such as antibiotic
resistance) to the host. Plasmids have been engineered to serve as vectors for the
propagation of DNA which is foreign to the host species.
Pleiotropy Multiple, apparently unrelated phenotypic effects of mutation at a
single gene.
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Point mutation A mutation affecting a single nucleotide pair. It can be used loosely
to mean mutations affecting a very small number of nucleotide pairs (perhaps up to
the insertion of a small mobile element such as an Alu element) or to the deletion of a
small number of nucleotide pairs.
Polyadenylation site The site at the 3´ end of a mRNA at which the mRNA has been
cleaved and a tail of 200 - 300 adenosine nucleotides has been added.
polygenic inheritance The inheritance of a characteristic which is determined by the
cumulative actions of many different genes, each with small individual effects.
Polymerase chain reaction (PCR) A technique by which a relatively small piece
of DNA of known sequence can be amplified (often from a complex mixture) by
successive cycles of strand separation followed by DNA synthesis (using a DNA
polymerase purified from a thermophilic bacterium) primed by artificially
synthesised oligonucleotide primers (one for each strand).
Poles The two ends of a spindle where the microtubules converge and to which
the chromosomes will eventually be pulled. They form around a structure known as a
centriole.
Polymorphism Genetic variation occurring in a population so that at least
two alleles are present at a frequency of 1% or gretaer. The variation may range from
alteration of noncoding DNA sequence without any phenotypic effect through many
possible intermediates to variation which gives rise to a visible change in the
visible phenotype.
Polypeptide chain The chain of aminoacids joined by peptide bonds which is the
primary product of the translation of the mRNA of a gene.
Polyploid Having more than the normal two haploid sets of chromosomes.
Positional cloning Identification of a gene from no more starting information than
its map position in the genome.
Primary constriction see centromere
Primary transcript The unmodified RNA product of
gene transcription before splicing has occurred.
Proband The affected member in a pedigree through whom the family came to
medical / scientific attention.
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Probe A DNA or RNA molecule which has been labelled and which may be used to
identify its complementary sequence by hybridisation.
Prokaryote A simpler organism than a eukaryote having no nucleus and being
different in many other ways too. e.g. a bacterium.
Promoter The DNA sequences at the 5´ end of a gene which are responsible for
binding RNA polymerase and transcription factors and which regulate the gene’s
expression.
Prophase A stage at the beginning of mitosis or meiosis during which
the chromosomes condense and become visible.
Proto-oncogene A gene which may mutate to become an oncogene.
Pseudogene A DNA sequence which resembles a gene but which has been inactivated
by mutation so that it cannot produce a functional product.
Pulsed field gel electrophoresis A technique of electrophoresis which is able to
resolve very large DNA molecules by periodic alterations of the direction of the
applied electric field.
q (see p!) in cytogenetics the long arm of a chromosome, in population genetics the
frequency of an allele (usually the less frequent of two).
Random mating Selection of a mate without considering their genotype or any trait
associated with a particular genotype.
Reading frame The way in which nucleotides are read in groups of three (codons) to
specify the polypeptide coded by a gene. An RNA molecule has three possible reading
frames - usually the most 5´ AUG codon defines the beginning of the reading frame
selected by the ribosomes. An open reading frame contains no in frame stop codons.
Recessive A mutation or allele which does not affect the phenotype unless it
is homozygous.
Reciprocal translocation A chromosomal rearrangement in which material is
exchanged between two nonhomologous chromosomes.
Recombinant A chromosome (or individual) arising from a crossover at meiosis.
Recombinant DNA DNA containing an artificial combination of pieces which are not
found together in nature.
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Recombination The formation of a new combination of linked alleles
by crossover at meiosis.
Recurrence risk The chance that a genetic disease may occur in siblings (or other
relatives) of an affected child.
Reduction division The first meiotic division in which the chromosome number is
reduced by half.
Repetitive DNA DNA sequences which are repeated more than once in
each haploid copy of the genome. See interspersed repetitive DNA, tandemly repeated
DNA and satellite DNA.
Restriction endonucleases, (restriction enzymes) Bacterial nucleases which cut
double stranded DNA at specific sites defined by short (4- 10bp) usuallypalindromic
sequences.
Restriction fragments The (relatively) short fragments of DNA which are the result
of the digestion of high molecular weight DNA by a restriction endonuclease.
Restriction fragment length polymorphism (RFLP) A common variation in DNA
sequence which manifests itself in the variation in length of one or morerestriction
fragments.
Restriction map A map showing the positions of restriction sites within a DNA
molecule.
Restriction sites Short, often palindromic DNA sequences which are the sites for
recognition by restriction endonucleases.
Retroposition The integration of a sequence derived from RNA into a DNA genome.
See retrovirus.
Retrovirus A class of viruses whose infectious genome is single stranded RNA and
which, as part of their normal life cycle, integrate into their host genome after
conversion of the RNA to DNA by the enzyme reverse transcriptase.
Reverse genetics An old name for positional cloning.
Reverse transcriptase A DNA polymerase which takes RNA as its template. It is
coded by a retrovirus gene.
(RFLP) See restriction fragment length polymorphism.
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Ribosome A ribonucleoprotein complex which translates mRNAs. See your
textbooks!
RNA The class of molecules which are the primary products of genes. One type of
RNA, mRNA carries the information coded in a gene from the nucleus to the
cytoplasm where it is translated into protein. See your textbooks!
RNA polymerase The enzyme which synthesises RNA from a DNA template.
Satellite DNA DNA containing a short sequence of nucleotides (5 - 200 bp) which
is tandemly repeated hundreds or thousands of times.
see minisatellite andmicrosatellite.
Segregation The separation of the alleles of a pair from each other at meiosis.
Selection The imposition of an external force onto an organism either naturally
(Natural selection) or experimentally so that some genotypes survive (and reproduce)
better than others.
Sense strand The DNA strand in a gene which has the same sequence as the primary
transcript. (see coding strand)
Sex Chromosome One of the chromosomes which are present in different numbers in
males and females. In humans this means the X and Y chromosomes, XX in females
and XY in males.
Sex-influenced A trait which is expressed to different extents from the
same alleles depending on the sex of the individual.
Sex-limited A trait which is not usually sex linked but is only expressed in one sex.
Sex-linked A trait which is caused by mutation of a gene on the X chromosome,
usually called X linkage to avoid confusion with Y linked traits.
Sib A brother or sister.
Sibship All the brothers and sisters in one family.
Silent allele An allele which has no effect on the phenotype.
Single copy DNA DNA whose sequence is present only once per haploid genome.
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Sister chromatid exchange A crossover between sister chromatids (chromatids
which are the products of replication of a single chromosome and which ought
therefore to be genetically identical).
Somatic cell A cell which is not on the lineage from which gametes are made.
(see germline)
Somatic cell genetics The study of genes using hybrids (fusions) between the somatic
cells of different species.
Somatic mutation A mutation which takes place in a somatic cell. It may give rise to
a clone of descendent cells each of which has inherited the mutation.
Southern Blot A technique named after Prof. Ed Southern in which,
after electrophoresis in agarose gels, DNA is transferred to a membrane where it can
be analysed by hybridisation with a probe. See blot
Spindle The structure of microtubules which pulls the chromosomes into the daughter
cells at anaphase in cell division.
Splice acceptor site The junction between the 3´ end of an intron and the
following exon.
Splice donor site The junction between the 3´ end of an exon and the
following intron.
Splicing Processing a primary transcript into a mRNA by removal of the introns. It
occurs within the nucleus.
Splice junction mutation A mutation which alters a junction between an intron and
an exon so that it no longer functions properly. This is likely to have a profound effect
on the coded polypeptide, splice donor site mutations lead to the retention of introns
in the mRNA, splice acceptor mutations lead to the skipping of the following exon.
Sporadic A case of genetic disease caused by a new mutation.
Stop codon One of the three codons (UAA, UAG, UGA) which cause chain
termination at the end of translation.
Structural gene A gene coding for a polypeptide or functional RNA product.
STS or Sequence Tagged Site A short region of genomic DNA which has been
sequenced and from which a PCR reaction has been designed which will allow its
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recognition in a DNA sample. STSs play an important role in the construction of
clone based maps and in mapping by the use of irradiation hybrids. An EST may be
an STS if it can be amplified from genomic DNA. Some STSs contain
a polymorphic microsatellite and can thus also be positioned on genetic linkage maps.
Synapsis The close pairing of homologous chromosomes in meiotic prophase which
enables crossovers to occur.
Synaptonemal complex The electron dense material which acts as a "zip fastener" to
hold together homologous chromosomes in meiotic prophase.
Syndrome A collection of symptoms which occur together and are thought to be
caused by the same mutation or chromosomal anomaly.
Synteny The presence of two genes on the same double stranded DNA molecule.
Tandem repeats Repeated sequences which are arranged consecutively and in the
same orientation.
Telomere The DNA structure which stabilises the ends of chromosomes.
Telophase The stage of meiosis or mitosis at which the chromosomes have reached
the ends of the spindle after division but the daughter cells have not yet taken
aninterphase appearance.
Teratogen A substance which can cause malformations of foetuses.
Termination codon see stop codon
Transcription The process of copying DNA into RNA mediated by the enzyme RNA
polymerase.
Transfection Transfer of DNA (usually of a gene) into a cultured cell where it can be
expressed.
Transgenic animal An animal (nearly always a mouse) into the genome of which a
foreign gene has been introduced.
Transition A mutation which has changed one purine (A, G) into the other, or one
pyrimidine (C, T) into the other. See transversion.
Translation The process of copying a mRNA into a polypeptide chain mediated by
the ribosomes.
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Translocation A mutation which has moved one segment of a chromosome to a
different position in the genome. A reciprocal translocation involves the exchange of
material between two chromosomes.
Transversion A mutation in which a pyrimidine is substituted for a purine or vice
versa. See transition.
Triploid A cell (or organism) having three haploid copies of the genome.
Trisomy having three copies of a single chromosome
Tumour suppresser gene A gene which if inactivated by mutation allows
uncontrolled cellular proliferation. Contrast with oncogene.
Unequal crossing over A crossover in which the chromosomal segments exchanged
are not equally sized because the breakpoint has occurred at a different place on each
homologue.
Uniparental disomy The inheritance of both copies of a single chromosome from one
parent (and neither copy from the other).
Upstream Genes have an orientation which is defined by their direction of
transcription (5' to 3'). Upstream means further in the opposite direction to the
direction oftranscription of a gene and even possibly beyond its beginning. (Opposite
is downstream.)
Vector (in DNA cloning) the molecule (plasmid, bacteriophage or artificial
chromosome) used to propagate a cloned DNA fragment.
VNTR (variable number of tandem repeats) A DNA polymorphism caused by the
presence of a variable number of short tandem repeated DNA sequences at alocus.
Western blot (see blot) Also known as Immunoblot. Proteins blotted onto a
membrane post electrophoresis. They can be detected there by appropriate antisera.
The name Western blot is a continuation of the Southern blot, Northern blot joke.
Wild type The normal allele at a locus in a population. It is usually a fully functional
allele. Equally, the normal phenotype.
X chromosome A chromosome which is present in two copies in the genome of
normal human females but in only one copy in normal males.
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X inactivation The random inactivation of all but one X chromosome in most cells.
See Barr body.
X linked A gene which is present on the X chromosome.
YAC, Yeast Artificial Chromosome A cloning vector based on a the essential
components of a yeast chromosome. It provides two telomeres, two selectable
markers and an origin of replication.
Y chromosome A small chromosome which, in humans, is present in one copy in
males only.
Y linked A gene which is present on the Y chromosome.
Zygote The diploid cell formed by the fusion of two haploid gametes. In humans. a
fertilised egg.
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