Chromosomal Inheritance Aberrations
I.
NORMAL INHERITANCE
A. The diploid number for humans is 46
1. We received 22 autosomal chromosomes and one sex chromosome from each
parent
B. Chromosomal inheritance aberrations include the following
1. Deficiencies
a) Monosomies and deletion aneuplodies
2. Duplications
a) Polyploidies and addtion aneuplodies
3. Inverstions
4. Translocation
II.TYPES
OF ABNORMAL CHROMOSOME INHERITANCE
A. Monoploidy
1. One set of each chromosome
2. 23 in humans
B. Polyploidy
1. Containing a complete extra set of chromosomes
a) Triploid
2. Causes
a) Usual cause (two thirds) is a single egg being fertilized by two sperms
b) Another cause is a diploid gamete being fertilized by a normal gamete
3. Symptoms
a) Lethal in humans, common in plants
(1) Fetus is usually aborted
(a) Accounts for 15% of spontaneous abortions
(2) A few survive a few days after birth, but have birth defects in almost all organs
4. Types
a) Autopolyploidy
(1) Extra set of chromosomes from the same species
(2) Causes
(a) Fertilization of an egg by more than one sperm
(b) Failure of chromosome to segregate during meiosis resulting in diploid
gametes
b) Allopolyploidy
(1) Extra set of chromosome from a different species
(2) These will usually be infertile due to problems of aligning non-homologous
chromosomes during meiosis
(a) A mule, arising from a horse and donkey, is infertile
(3) An example is wheat
(a) Has three sets of chromosomes
(i) Two sets from primitive wheat and one set from goat grass
5. Mendelian ratios
a) Even number of homologous chromosomes
(1) Each gamete will receive a pair of homologous chromosomes from a tetraploid
(a) AAAA (gamete = AA) X aaaa (gamete = aa) = AAaa
(b) AAaa (gametes = AA, Aa, Aa, Aa, Aa, or aa) X AAaa = 1 AAAA, 8 AAAa,
18 AAaa, 8 Aaaa, 1 aaaa
b) Odd numbers of homologous chromosomes
(1) Not all homologous chromosomes can pair in triploids
(a) Hence they are usually sterile
(2) Half of bananas' gametes will be haploid, and half will be diploid
(a) Bananas are sterile, produce no seeds, and are propagated vegetatively
(3) A triploid alloploid
(a) Possible gametes
(i) CCBB, CBB, CCB, CB
(b) Possible offspring
(i) 1 diploid, 1 tetraploid, 4 triploid, 10 aneuploids
C. Aneuploidy
1. Either containing extra chromosomes or missing chromosomes
a) Trisomy
(1) Having an extra chromosome
b) Tetrasomy
(1) Having two extra homologs
c) Monosomy
(1) Missing a chromosome
d) Nullisomic
(1) Lost both homologs
2. Caused by meiotic nondisjunction
a) Types of meiotic nondisjunction
(1) Failure for homologous chromosomes to separate during anaphase I
(a) This will result in two gametes receiving extra chromosomes and the other
two not receiving a full chromosome compliment
(2) Failure for sister chromatids to separate during anaphase II
(a) This will result in one gametes receiving extra chromosomes, one two not
receiving a full chromosome compliment, and two gametes with 23
chromosomes each
3. Symptoms
a) Autosomal trisomy children are usually severely mentally retarded
b) Sex chromosome trisomy
c) Monosomies rarely survive to birth
D. Deletion
E.
F.
G.
H.
1. Part of a chromosome missing
2. Location
a) Telomeres
(1) When an end of a chromosome breaks off and does not fuse bake
b) Interstitial
(1) A chromatid breaks in two places, the ends fuse together, but the middle
piece is lost
c) Break point effect
(1) Break is in the middle of a gene
(2) This will result in a truncated protein
d) Position effect
(1) Joining of two unrelated areas
3. Cri du chat (cat's cry syndrome)
a) Deficiency of portion of the fifth chromosome
b) Symptoms
(1) Severe mental retardation
(2) Sounds infants make resembles a cat's cry
Duplication
1. This is when a chromosomal segment occurs more than once in the same
chromosome
2. This may be due to a broken segment attaching to its homologous chromosome
or due to unequal crossing-over
Inversion
1. A section of chromosome turned around 180 from its normal orientation
2. This leads to abnormal crossing-over and altered gene activity
Translocation
1. Chromosomal segment is moved between non-homologous chromosomes
2. In 5% of cases, a translocation between chromosomes 21 and 14 is the cause of
Down syndrome
Isochromosomes
1. Chromosomes contain identical arms due to problems during anaphase II
2. The chromosome splits in the wrong plane
III.AUTOSOMAL
CHROMOSOME ANEUPLOIDY
A. Aneuploidy can occur for each chromosome, but only 9 appear in newborns
1. The rest result in spontaneous abortions
a) It is estimate that 50% of spontaneous abortions are caused by aneuploidy
B. Trisomy 21 (Down syndrome)
1. Inheritance of 3 chromosomes 21
a) One chromosome 21 from one gamete and two from the other gamete
(1) Most common trisomy of newborns
(2) 90% of trisomy 21 is due to nondisjunction in meiosis one in females; about 10
% is due to nondisjunction in meiosis 1 or 2 in males
b) May also be caused by translocation of part of chromosome 21 to another
chromosome (usually chromosome 14)
2. Chances of having a down syndrome child increases as the mother ages
a) As a women ages, her body is less likely to spontaneously abort trisomy 21
embryos
(1) Examples: Under 30 chances are 1:952; at age 35 it is 1:378; at age 40 it is
1:106, and at age 45 it is 1:14
3. Signs and symptoms
a) Rounded face, epicanthal folds (Oriental-like fold of eyelids), enlarged
tongue, and mental retardation
(1) The level of mental retardation varies greatly
(2) Life expectancy can be into the thirties
(3) The Gart gene, located on the bottom third of chromosome 21, leads to a high
level of blood purines and may account for the mental retardation
C. Trisomy 18 (Edward Syndrome)
1. Symptoms
a) Heart defects, displaced liver, growth retardation, oddly clenched fists, short
long toes, abnormal or absent finger prints, fused second and third toes,
severe mental retardation, etc.
b) Less than 5% survive one year after birth
2. Causes
a) Nondisjunction of chromosomes 18 during meiosis II during oocyte
formation
D. Trisomy 13 (Patau Syndrome)
1. Symptoms
a) Fusion of eyes (one large eye results) or small or absent eyes, major organ
deformities, often have extra fingers or toes
b) Less than 5% survive one year after birth, with only a few reaching adult
hood
(1) Mental development does not proceed past 6 months
IV.SEX
CHROMOSOME ANEUPLOIDY
A. Humans are more tolerant to sex chromosome trisomy than to autosomal trisomy
1. The extra X chromosome is deactivated as an extra Barr body
2. The Y chromosome has few genes
B. Patterns
1. Females can produce eggs with either two X chromosomes (XX) or no X
chromosomes (OO) due to a single meiotic nondisjunction event
a) In an unlikely event of two nondisjunction event during the same egg
development, and egg could contain up to 4 X chromosomes
2. Males may produce sperm with either no sex chromosomes (OO), two X
chromosomes (XX), both an X and Y chromosomes (XY), or two Y chromosomes
(YY)
C. Female nondisjunction
1. Turner syndrome (45,X)
a) With only one X chromosome (XO)
(1) 99% of effected fetuses are spontaneously aborted
(2) Sex will be female
b) One in 2,000 females are born with this condition
(1) Often not detected to puberty
(a) Mental abilities seem normal and side effects are not great if given
hormonal treatment
(2) The female has a bull neck, short stature, nonfunctional ovaries, no puberty or
menstruation and immature sexual features, folds of skin on their necks and
back
2. Metafemale (47,XXX)
a) With 3 X chromosomes (XXX), these females usually have no apparent
physical abnormalities except tallness and menstrual irregularities
b) Nuclei will contain two Barr bodies
3. Klinefelter syndrome (47,XXY)
a) With XXY genotype, the males have underdeveloped testes, some breast
formation, and may have subnormal intelligence
b) Symptoms may not be severe and not detected until infertility problems
arise
4. 45,Y
a) Non-viable
D. Male nondisjunction during Meiosis I
1. Turner syndrome (45,XO)
a) See above
2. Klinefelter syndrome (47,XXY)
a) See above
E. Male nondisjunction during Meiosis II
1. Metafemale (47,XXX)
a) See above
2. Jacobs Syndrome (47,XYY)
a) Effects about 1 in every 1000 men
b) Symptoms include tallness and otherwise may be normal
(1) Old studies indicated that men with this conditions are more likely to become
criminals, but this has later been shown not necessarily to be true
3. Turner Syndrome
a) See above
V.
DELETIONS
A. Cri-du-chat (5p- syndrome)
1. A portion of chromosome 5 is deleted
a) Such individuals meow like a kitten when they cry and may have mental
retardation (depending upon the amount of chromosomal material missing)
VI.DUPLICATIONS
A. If genes are only duplicated one or twice symptoms may be mild
B. If genes are repeated many times severe mental retardation and development
problems may arise
VII.TRANSLOCATION
A. Reciprocal translocation
1. Cause
a) Non-homologous chromosomes exchange parts
2. Effects
a) If the translocation does not break any genes, the person may be normal,
but would be a translocation carrier
b) If the translocation does disrupt a gene, symptoms will vary depending upon
the effected gene
B. Robertsonian translocation
1. Cause
a) The short arms of two non-homologous chromosomes break and the two
remaining large arms adhere
b) The short arms are repeated elsewhere, so their absence is not usually a
problem
2. People with this condition are called translocation carriers and have 45
chromosomes
3. Symptoms
a) Range from mild to severe depending upon which genes may have been lost
b) Reproductive trouble as there will be no homologous chromosomes to line
up with
4. Robertsonian translocation accounts for 5% of Down syndrome cases
a) Part of chromosome 21 is translocated to another chromosome (usually
chromosome 14)
(1) This type of Down syndrome can be genetically passed on and is not age
related
5. Robertsonian translocation is also responsible for cases of Patau syndrome
a) Part of chromosome 13 is translocated to chromosome 14
VIII.INVERSION
A. Types
1. Paracentric inversion
a) Does not involve the centromere
b) Results in two normally functioning chromosomes and two abnormal
chromosomes
(1) Dicentric chromosome
(a) One abnormal chromosome contains two centromeres
(i) This chromosome is broken apart during mitosis as the two
centromeres are pulled towards opposite poles
(2) Apocentric chromosome
(a) The other abnormal chromosome lacks a centromere and is lost during
cell division
B. Symptoms
1. Only 5 - 10% of individuals with inverted chromosomal segments will show
symptoms
a) Of these, symptoms will vary depending upon the gene(s) disrupted
IX.ISOCHROMOSOMES
A. Cause
1. During anaphase II of meiosis, chromosomes split in the wrong plane
a) This results in chromosomes with identical arms
X.
OTHER
A. Fragile X Syndrome
1. The X chromosome is nearly broken and the tip hangs by a flimsy thread
2. Symptoms
a) Children may be hyperactive, speech delayed, adults have large testes and
protruding ears and jaw
3. This is more common in males, since females receive two X chromosomes and
males only one
a) Seen in both sexes but less severe in females