LECTURE 014v2 Chromosomal Basis of Inheritance
1. CHROMOSOMAL BASIS OF INHERITANCE
A. “TETRAPLOID RAT”
2. ALTERATIONS IN CHROMOSOME SETS
A. Polyploidy: A chromosomal alteration in which the organism possesses more
than two complete chromosome sets.
B. Triploidy: A type of polyploidy.
3. Alterations in Chromosome Number
A. Down syndrome: an aneuploidy involving human chromosome number 21.
More accurately called trisomy 21.
B. Aneuploidy: a chromosomal abnormality in which one or more chromosomes
are present in extra copies or are deficient in number.
C. Turner syndrome: 45,X, is a monosomy.
4. CHROMOSOMAL BASIS OF INHERITANCE
A. FISH: fluorescence in-situ hybridization
B. Two signals because chromosomes are replicated and have two
___________????
5. DNA PROBE: A purified fragment of DNA labeled with a radioactive isotope or
fluorescent dye and used to identify complementary sequences by means of
hybridization.
A. CHROMOSOME PAINTING of a DIPLOID GENOME
B. IDENTIFICATION OF A TRANSLOCATION
C. USING CHROMOSOME PAINTING
6. CHROMOSOMES
A. Chromosomes first visualized in 1842 in plants
B. Mendel’s work: started1857
C. Mitosis: 1875
D. Meiosis: 1890
E. Sutton, Boveri and others: 1902 Chromosome Theory of Inheritance
F. 1907 Thomas Hunt Morgan and “The Fly Room”.
G. Chromosome Theory of Inheritance: a basic principle in biology stating that
genes are located on chromosomes and that the behavior of chromosomes
during meiosis accounts for INHERITANCE PATTERNS.
7. LAW OF SEGREGATION AS TOLD BY CHROMOSOMES
A. Following of one gene (one character) with Mendel’s sweet peas AND the
chromosomes for that character.
B. The two alleles for each gene separate during gamete formation. See R and
r. (Could be R and R or r and r.)
8. LAW OF INDEPENDENT ASSORTMENT AS TOLD BY CHROMSOMES
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A. Following of two genes (two characters) with Mendel’s sweet peas AND the
different chromosomes for those characters (see R and Y).
B. Alleles of genes on nonhomologous chromosomes assort independently
during gamete formation.
9. The search for a variant….
A. “Two years’ work wasted. I have been breeding those flies for all that time
and I’ve got nothing out of it.”
B. Thomas Hunt Morgan
10.
SEX-LINKED DISORDERS HAVE A DIFFERENT INHERITANCE PATTERN
A. Thomas Hunt Morgan: “The fly room” and the correlation between a
particular trait and an individual’s sex. Evidence that a specific gene is
carried on a specific chromosome.
B. WILD TYPE: an individual with the phenotype most commonly observed in
natural populations also refers to the phenotype.
11.
A.
B.
C.
D.
E.
F.
G.
12.
13.
DROSOPHILA MELANOGASTER
A. Conclusion: Morgan deduced that this eye color gene is located on the X
chromosome and that there is no corresponding locus on the Y chromosome.
B. A female could have white eyes if both of her X’s had the recessive mutant
gene. Not possible in this case because all of the father’s of the F1 were red
eyed.
A.
B.
C.
D.
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DROSOPHILA MELANOGASTER
One of first model organisms for research. WHY?
Short life cycle!
Simple to culture.
Simple to cross! Single mating produces hundreds of offspring.
Only 4 pairs of chromosomes, 3 pairs of autosomes and one pair of sex
chromosomes.
Sex is determined by X and Y sex chromosomes. 2 X’s determine female, 1
X results in male.
Mutant phenotypes regularly arise or are induced.
SOME CHROMOSOMAL SYSTEMS OF SEX DETERMINATION ARE DIFFERENT
Fruit flies are not the only organism with a unique pattern of sex
determination.
Humans XX or XY. In mammals sex of offspring depends on whether the
sperm contains an X or a Y chromosome.
Grasshoppers, cockroaches, and some other insects, there is only one type
of sex chromosome and it is an X. Females are XX and males have only one
sex chromosome: X. Sex is determined if the sperm contains an X or no sex
chromosome.
Birds, some fishes, some insects the sex chromosomes present in the egg,
not the sperm, determine the sex of the offspring: females are ZW and
males are ZZ.
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E. Bees & ants: There are no sex chromosomes in most species of bees and
ants. Females develop from fertilized eggs and are ♀: diploid. Males develop
from unfertilized eggs and are haploid, they have no fathers. ♂:haploid
14.
15.
HUMAN SEX CHROMSOMES
A. Human sex chromosomes contain a differential region and two pairing
regions.
B. Pseudoautosomal region (PAR): The regions are homologous, autosomallike.
C. Important for correct disjunction at meiosis and crossing over.
SYNAPSIS OF THE X AND Y
16.
PATTERN OF SEX DETERMINATION IN HUMANS
A. In humans, the anatomical signs of sex begin to emerge around 2 months of
embryological age. Before that, the rudiments of the gonads are generic;
they can develop into either testes or ovaries.
B. This depends on whether the Y is present or not.
17.
Y-LINKED INHERITANCE
A. Holandric: Refers to Y-linked inheritance; a transmission exclusively from
father to son.
B. Only ~78 holandric genes have been identified.
C. In the absence of those proteins, an XY individual is male, but does not
produce normal sperm.
D. SRY gene (Sex-determining Region on the Y) is expressed during embryonic
development and instrumental in the developmental cascade leading to male
differentiation.
18.
GENE DOSAGE AND BARR BODIES
A. X-inactivation: Inactivation of most of the genes on one X chromosome in
the somatic cells of female mammals.
B. All female mammals (including humans) have 2 X chromosomes.
C. One X has all of its genes active, all other X’s, IF PRESENT, are “turned off”
in every cell. This provides for equal amounts of protein products produced
from genes in the X-chromosomes of males and females.
19.
Genetics Problems
A. Neither Tim nor Rhoda has Duchenne muscular dystrophy, but their firstborn
son does. What is the probability that a second child will have the disease?
What is the probability if the second child is a boy? A girl?
20.
X-INACTIVATION
A. X-inactivation is random.
B. Occurs on the X-chromosome from the father or the mother.
C. Inactivation passes to all cell descendents. Occurs early in embryonic life
around the time of implantation (7-10 days after fertilization.
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D. Females are considered mosaics for the X chromosome: Paternally or
maternally inactivated or activated.
E. Males are hemizygous for the X chromosome: “hemi” meaning half.
21.
A.
B.
C.
D.
E.
48, XXXX
What if a female is 48, XXXX? How many Barr bodies will she have? THIS
PATIENT: Mentally deficient.
Why does she still have abnormalities?
Approximately 12 genes remain active on the inactivated chromosome.
GENE: XIST
Active only on the X chromosome that will become the Barr body. Appears to
initiate x-inactivation.
22.
X-INACTIVATION
A. In 1961 Lyon described: selection of which X chromosome will form the Barr
body occurs randomly and independently in each embryonic cell present at
the time of inactivation.
B. The LYON HYPOTHESIS: Genes from one X-chromosome in each cell of the
female embryo are rendered transcriptionally inactive.
C. English Geneticist: Mary Francis Lyon. Born May 15, 1925. Retired from
active research in 1990.
23.
X-INACTIVATION AND CATS
A. If females are heterozygous for an x-linked trait, about half of her cells will
express one allele, while the others will express the alternate allele, even
though she has both in the cell.
B. Remember, one has been inactivated.
24.
Hypohidrotic Ectodermal Dysplasia – remember from the start of the
semester? Males without sweat glands.
25.
X-INACTIVATION AND HUMANS
A. ANHIDROTIC ECTODERMAL DYSPLASIA
B. When alleles on two homologous X chromosomes are not identical,
differences can occur in “patches” throughout the body.
C. Human females with this disorder are heterozygotes for a recessive allele
that causes the absence of sweat glands.
26.
LINKAGE – JUST TO FURTHER COMPLICATE MATTERS
A. LINKED GENES: Genes close enough together on a chromosome that they
TEND to be inherited together.
B. In these crosses, Morgan observed a much higher proportion of parental
phenotypes than would be expected if the two genes assorted
independently.
27.
What would independent assortment look like?
28.
THE ALL IMPORTANT TESTCROSS
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A. TESTCROSS: Breeding an organism of UNKNOWN GENOTYPE with a
HOMOZYGOUS RECESSIVE individual to determine the unknown genotype.
The ratio of phenotypes in the offspring reveals the unknown genotype.
29.
THE UNLIKELY EVENT OF CROSSING OVER BETWEEN LINKED GENES
A. The expected ratio would be 575 of each parental and 575 of each
recombinant when genes exist on different chromosomes or are very far
from each other.
B. A 50% recombination frequency indicates UNLINKED GENES.
C. These results indicate LINKED GENES, because 17% of the time.
30.
MAPPING GENES USING REC0MBINATION
A. GENETIC MAP: An ordered list of genetic loci along a chromosome.
B. LINKAGE MAP: A genetic map based on the FREQUENCIES OF
RECOMBINATION between markers during crossing over of homologous
chromosomes.
C. MAP UNITS: a unit of measurement of the distance between genes. One map
unit is equivalent to a 1% recombination frequency.
31.
PARTIAL LINKAGE MAP Drosophila
A. A few of the genes mapped on Drosophila chromosome #2.
B. The number at each gene locus represents the map distance between that
trait and aristae (at zero).
C. Notice at 104.5 another gene that can affect eye color.
32.
Genetics Problems
A. Genes A, B, and C are located on the same chromosome. Testcrosses show
that the recombination frequency between A and B is 28% and the
recombination frequency between A and C is 12%. Can you determine the
linear order of these genes?
33.
ABNORMAL CHROMOSOME NUMBER
A. Large-scale chromosomal changes can affect an organism’s phenotype.
B. Physical and chemical disturbances, as well as errors in meiosis can damage
chromosomes in major ways.
C. 60% of first trimester miscarriages in human beings are chromosomally
abnormal.
D. Plants tolerate genetic defects to a much greater extent.
34.
DOWN SYNDROME (trisomy 21)
A. Down syndrome can not be diagnosed by ultrasound
35.
MONOSOMICS (2n – 1) Turner Syndrome
A. Monsomics are missing one copy of a chromosome.
B. In most diploid organisms, the absence of one chromosome copy is
deleterious.
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C. 45, X is Turner syndrome: characteristic sterility, short stature, barrel chest,
poor breast development, widely spaced nipples, webbing of neck, near
normal intelligence.
36.
A.
B.
C.
D.
TURNER SYNDROME: 45,X
Results from the presence of a single X chromosome.
Usually, paternal X is missing.
99% of these fetuses end in miscarriage.
Many surviving individuals are likely mosaics.
37.
KLINEFELTER SYNDROME, XXX females (no image) XYY MALES
A. Do Klinefelter males (47,XXY) have a Barr body?
B. XYY males have a controversial history. Research attempts have been made
to link it to a predisposition to violent behavior. Having an XYY male does
not guarantee this phenotype. Most of these males are fertile, with normal
gametes.
C. 47, XXX are phenotypically normal females generally, with tall stature and
normal fertility, normal gametes.
38.
TRISOMY 18, Edwards Syndrome
A. Physical attributes of trisomy 18 include characteristic clenching of hands,
abnormal ear development, heart defects, rocker bottom feet, small pelvis,
micrognathia (small jaw), severe mental retardation.
B. Average life span is 51 days after birth if birth occurs.
39.
PATAU SYNDROME, Trisomy 13
A. Characteristics of trisomy 13: small malformed head, cleft lip and or palate,
heart defects, polydactyly, severe mental and physical handicaps.
B. One case of an individual living into childhood – most die in less than 1 year.
40.
A.
B.
C.
D.
E.
F.
41.
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ALTERATIONS OF CHROMOSOME STRUCTURE
Errors in meiosis, damaging agents such as radiation can cause breakage of
a chromosome.
This can cause several types of changes in chromosome structure.
DELETION: occurs when a chromosomal fragment is lost. It can be part of a
gene, an entire gene or several genes. If the centromere is deleted, the
chromosome will be lost (Monosomies).
DUPLICATION: The deleted fragment may become attached as an extra
segment to a sister chromatid, and this produces duplication. It can also be
faulty replication that produces duplication.
INVERSION: a chromosome fragment may also reattach to the same
chromosome, but in reverse orientation causing an inversion.
A fragment can also join a NONHOMOLOGOUS chromosome and create a
rearrangement we call a translocation.
DEFINITIONS
A. CHROMOSOME MUTATIONS: Any type of change in chromosome structure or
number.
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B. Chromosome mutations are visible with a microscope versus gene
mutations, which are not.
C. Chromosome mutations can be detected by genetic or molecular analysis.
D. Think reading frame!
E. Chromosome painting demonstrates a translocation.
42.
A.
B.
C.
D.
E.
F.
43.
5
XY FEMALES caused by ALTERATION OF CHROMOSOME STRUCTURE
Androgen insensitivity syndrome.
Rare X-linked recessive phenotype.
1/65,000 male births.
Mutation in the androgen-receptor gene on the X chromosome. Male
hormone can not masculinize male organs.
One sister was XX, but a carrier (like mother), and gave birth to an XY male.
Spanish athlete Maria Jose Martinez Patino at the Olympics
Cri du chat: Loss of the tip of the short arm of one homolog of chromosome
A. Cat like cry, microcephaly, moonlike face, hypertelorism, mental retardation.
44.
GENOMIC IMPRINTING
A. GENOMIC IMPRINTING: a phenomenon in which a gene inherited from one
of the parents is not expressed, even though both gene copies are
functional.
45.
GENOMIC IMPRINTING
A. Imprinting of the Igf2 gene in mice.
46.
GENOMIC IMPRINTING
A. Sex specific imprinted alleles express only maternal or paternal copy.
B. Germ cells erase imprint from your parents.
47.
GENOMIC IMPRINTING
A. Imprinting established in gametes in a sex specific manner.
B. After fertilization, imprint controls gene expression is somatic tissues of
embryo.
C. Persists into adulthood.
48.
49.
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A.
B.
C.
D.
E.
F.
PRADER-WILLI SYNDROME
Dysmorphic syndrome
Mental Retardation
Obesity, excessive, indiscriminate eating habits (McDonalds, locks)
Small hands and feet.
Short stature hypogonadism.
~70% of cases: deletion of 15q11-q13 on chromosome inherited from
father.
ANGELMAN SYNDROME
A. Unusual facial appearance.
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B. Severe mental retardation.
C. Short stature, spasticity, and seizures.
D. ~70% of cases, deletion of 15q11-q13 on chromosome inherited from
mother.
E. Parental origin of genetic material has a PROFOUND effect on the clinical
expression of a defect.
50.
INHERITANCE INDEPENDENT OF THE NUCLEUS
A. Distinct and specialized subset of the genome is found in the mitochondria,
(of plants, also) as well as plant chloroplasts.
B. Inherited independently of the nuclear genome.
C. Called “extranuclear inheritance”.
51.
A.
B.
C.
D.
E.
F.
UNIPARENTAL INHERITANCE
Organelle chromosomes located in the cytoplasm.
Male and female gametes do not contribute cytoplasm equally to the zygote.
Organelle genes demonstrate uniparental inheritance.
Progeny inherit organelle genes exclusively from one parent and not the
other.
Most often maternal inheritance.
Maternal inheritance: A type of uniparental inheritance in which all progeny
have the genotype and phenotype of the parent acting as the female.
52.
mtDNA, cpDNA
A. mtDNA = mitochondrial DNA
B. cpDNA = chloroplast DNA
53.
CYTOPLASMIC MUTATIONS IN HUMANS
A. MUTATION RATE: Ten times higher than that of nuclear DNA. Why?
B. Inefficient DNA repair mechanisms.
C. Possible damage from free oxygen radicals released during oxidative
phosphorylation process utilized to produce ATP.
54.
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A.
B.
C.
D.
E.
F.
MITOCHONDRIAL DISORDERS KEARNS-SAYRE, MELAS
Kearns-Sayre disease
Muscle weakness
cerebellar damage
heart failure
MELAS: mitochondrial encephalo-myopathy and stroke-like episodes
Single base tRNA mutation
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