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

XX

1st division 2nd division

Egg X1st polar body X

2nd polar body X2nd polar body X

Sex Chromosome Abnormalities

• non-disjunction of X chromosomes at meiosis I in female

XX

1st division 2nd division

Egg XX polar body XX

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

XY

1st division 2nd division

XX

YY

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 sperm meets X egg to produce XXY male

XYXY

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

• 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

• Genotype male female

• H’H’ Horns Horns

• H’H Horns No horns

• HH No horns No horns