Transcript Sex Chromosome Abnormalities

Sex Chromosome Abnormalities
• Occur during non-disjunction of X or Y
chromosomes at meiosis I or meiosis II
• Normally in meiosis to produce eggs,
the two X’s pair at meiosis I
Egg X
1st polar body X
X
X
2nd polar body X
2nd polar body X
1st division
2nd division
Sex Chromosome Abnormalities
• non-disjunction of X chromosomes at
meiosis I in female
Egg XX
polar body XX
X
X
1st division
2nd division
XX eggs fertilized by X sperm give Triple X female;
XX eggs fertilized by Y sperm give XXY male
Sex Chromosome Abnormalities
• Occur during non-disjunction of X or Y
chromosomes at meiosis I or meiosis II
• Normally in meiosis to produce sperm, a
small part of the X and Y pair
X
X
X
Y
Y
Y
1st division
2nd division
Sex Chromosome Abnormalities
• Occur during non-disjunction of X or Y
chromosomes at meiosis I or meiosis II
• Non disjunction in meiosis to produce sperm,
can cause: XX, XY, YY or O sperm
X
Y
XY
XY
XY sperm meets X egg to produce XXY male
Triple X females- (47 XXX)
• Fertile; tend to have XX or XY offspring
• Normal IQ range
– 75% slow in learning reading, math
– tendency for anxiety
• frequency in population is about 1/ 4,000
live births
• also called triplo X
Turners syndrome females (45 XO)
– sterile
– Turners syndrome females are under 5’
and usually normal IQ
– difficulty in 3D rotation tests
– heart and kidney problems; frequency
1/2,000 live births
– Estrogen helps for secondary sex
character development
– HGH allows increase in stature
– about 1 in 2,500 female births
Klinefelter Males (47 XXY)
• Taller than average; infertile; small
testes
• At puberty some breast development is
easily treated with testosterone but
does not restore fertility
• Occurs 1 in 500 to 1000 male births
XYY males
• Taller than average; acne worse than
average; normal IQ
• XYY males are fertile; have XX or XY
children
• Frequency 1 in 300 to 1 in 1000 births
• Slight increase of XYY individuals in
prison population per capita
Sex Determination in humans
• Presence or absence of Y at fertilization
determines sex of fetus; Y chromosome will
produce male; no Y means female phenotype
will result
• same special mass of cells in very early
embryo develops into ovary (XX) or testes
(XY)
• By 7 weeks embryo is ready to develop into a
male or a female individual
Y chromosome genes
• The Hy gene on the Y chromosome
codes for the Hy antigen protruding
from the surface of all male cells.
• After 7 weeks Tdf (Sry) gene on the Y
chromosome is expressed. The product
of this gene directs some of the
ovotestes cells to develop into the
testes and to start making testosterone
Mullerian and Wolffian ducts
• Ovaries in XX embryos begin to develop in
first few weeks;
• In XY embryos, the starting at 7 weeks,
ovotestes cells will develop into Wolffian
ducts, a system of ducts connecting the
testes and urinary system in males
• Ovotestes cells form Mullerian ducts in XX
embryos; ducts develop around 11 weeks,
eventually forming oviducts and uterus,
connecting the ovaries to the vagina
Primordial gametes form
outside embryo about 14 d.
• The future sperm and egg cells are
never a part of the embryonic tissue.
• These primordial cells arise separately
and do not undergo any differentiation
as the other embryonic cells do.
• Primordial gametes migrate into
developing ovaries and testes.
At puberty secondary sex
changes occur
• Hormones prepare body for reproduction.
• Gonadotropic hormones, FSH and LH start
menstrual cycle each month, causing
maturation of egg
• FSH and LH present in trace amounts in
males cause beard to form, Adam’s apple to
enlarge, facial bones to grow, etc.
• Adrenal glands secrete
Guevedoces syndrome in XY
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•
•
•
XY infants lack enyme 5H reductase
Fail to develop external male genetalia
Phenotype is female at birth
About age 12, the enzyme appears and
the penis and testes develop and by
age 20 these individuals are fully
developed males
Many hormones produced by
biosynthetic pathways
• Testoterone and estrogen are formed from
the cholesterol biosynthetic pathway
• Many enzymes (proteins) are required to
catalyze the reactions in pathway; genes for
these enzymes on autosomes not on X or Y
• Many mutations affect sexual development by
disrupting hormone formation
Tfm, an X-linked gene
• Tfm gene codes for protein that sticks out of
cells and binds testosterone
• In XtfmY males normal development of sex
characteristics is not possible because cells
are not affected by testosterone
• Phenotype of Tfm XY is sterile female; no
penis; testes form but remain up in the body;
may be surgically removed to lower risk of
cancer
• Also called Complete Androgen Insensitivity
Brain-sex
Perception of gender
• Tfm individuals perceive themselves as
female from earliest memories;
Guevedoces individuals perceive
themselves as male from earliest
memories.
• Tfm individuals are treated with
estrogen to stimulate female
characteristics
Sex-related inheritance
• Barr bodies are condensed (inactive) X
chromosomes found in interphase
nuclei
• In nuclei with two X chromosomes, one
X becomes inactivated and appears as
a blob in the nucleus when stained
Lyon Hypothesis:
• the condensed X is inactive.
• X-inactivation occurs early in
development
• Inactivation of one of the X’s is random
• The same X remains inactive in all
daughter cells throughout cell divisions
• On 50th anniversary, called “Lyons Law”
Lyon hypothesis explains:
• Dosage compensation; XCfXCf and XCfY
genotypes will show same amount of clotting
factor protein in blood as males.
• Why females heterozygous for X-linked trait
can vary greatly in gene expression
• e.g. tortoise shell cats and calico cats are
always XBXb females; orange patches are
where Xb is active, black patches where XB is
active
Tortoise shell cat
Calico cat
• Calico cats also express dominant gene
for white spotting.
Genomic Imprinting
• Small regions of AUTOSOMES are
inactivacted during formation of egg and
sperm (gametogenesis)
• Inactivated regions not expressed in
fetus but gene donated from other
parent is normally active
• If other parent donates a defective
gene, aberrant phenotype results
Prader-Willi and Angelman
• Both syndromes are related to failure of
gene expression on chromo. 15
• Prader-Willi: mental retardation, hunger
uncontrolled causes obesity
• Angelman syndrome: severe speech
impairment, mental retardation, happy
demeanor, sleep disorders
Sex-limited traits
• Genes are in both sexes but only
expressed in one of the sexes
• Genes usually not on X or Y
chromosomes; usually on autosomes
• Examples: lactation in female mammals
Sex-influenced traits
• Dominant in one sex, recessive in the
other
• Examples: horns in male sheep, pattern
baldness in human males
• Must use chart with genotype and sex
to determine outcome or phenotype
Horns in sheep
• H’H heterozygote gives different phenotype
depending on sex; sex hormones involved
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Genotype
H’H’
H’H
HH
male
Horns
Horns
No horns
female
Horns
No horns
No horns