Sex Chromosome Abnormalities

1
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 Xs
  pair at meiosis I

Egg X 1st polar body X 2nd polar body X 2nd
polar body X
X X
1st division 2nd division
2
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
3
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 Y Y
X Y
1st division 2nd division
4
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

XY XY
X Y
XY sperm meets X egg to produce XXY male
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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

6
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

7
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

8
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

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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

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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

11
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

12
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.

13
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, Adams apple to enlarge,
  facial bones to grow, etc.
• Adrenal glands secrete

14
Guevedoces syndrome in XY

• 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

15
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

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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

17
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

18
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

19
Lyon Hypothesis

• the condensed X is inactive.
• X-inactivation occurs early in development
• Inactivation of one of the Xs is random
• The same X remains inactive in all daughter cells
  throughout cell divisions
• On 50th anniversary, called Lyons Law

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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

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Tortoise shell cat
22
Calico cat

• Calico cats also express dominant gene for white
  spotting.

23
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

24
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

25
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

26
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

27
Horns in sheep

• HH heterozygote gives different phenotype
  depending on sex sex hormones involved
• Genotype male female
• HH Horns Horns
• HH Horns No horns
• HH No horns No horns