SEX DETERMINATION from these studies concluded that genes are on chromosomes and specialized chromosomes determine sex.

SEXSEXDETERMINATIONDETERMINATION

• from these studies concluded that genes are on chromosomes and specialized chromosomes determine sex

Modes of Sex Determination

• XX/XY (ZZ/ZW) (Lygaeus)

- heteromorphic sex chromosomes

• XX/XO (Protenor)

heteromorphic chromosomes

- a chromosome pair with some homology, but differing in size, shape or staining properties

heterogametic sex (e.g. XY OR ZW)

- the sex with different sex chromosomes; the gametes have different sex chromosomes …..the opposite of homogametic sex

Human Males have Heteromorphic Human Males have Heteromorphic Sex ChromosomesSex Chromosomes

XY Method of Sex DeterminationXY Method of Sex Determination

XY method common in higher organisms

Y-chromosome evolved to give X a pairing partnerA = autosome, any non sex-chromosome

Y

XY

XY XX

X

A

X

Sex Determination in HumansSex Determination in Humans

(X)

XXX XXY XO YO

Primary non-disjunction

Aneuploid OffspringAneuploid Offspring

XXX -- Trisomy-X

XXY -- Klinefelter

XO -- Turner

YO -- Dies

• aneuploidy involving the sex chromosomesis much better tolerated than autosomal aneuploidy

XXX SyndromeXXX Syndrome

47, XXX female (also see XXXX and XXXXX)

1/1200 female live births

Variable phenotype, frequently appear normal, sterile, may show mental retardation. Under-developedsecondary sex characteristics

Klinefelter SyndromeKlinefelter Syndrome

47, XXY male (XXXY, XXXXY, XXYY)

1/500 male live births

Male genitalia, testes undeveloped,fail to produce sperm

Female secondary-sex characteristics

Turner SyndromeTurner Syndrome

45, XO female

1/2000 female live births

Ovaries rudimentary, sterile

Short stature, shield-like chest,webbed neck

Normal intelligence

Many XO fetuses miscarry

XYY ConditionXYY Condition

47, XYY male

1/1000 male live births

Above-average height, 2% in maximum securityprisons are XYY, personality disorders, subnormal intelligence

Fertile

Most XYY males socially normal

Human Sex-Determination Human Sex-Determination MechanismMechanism

XY XOXXY XXXYY XXXXXYY XXXXXXXY XXXXXXXXXY

Presence of Y is male-determining

Lack of Y is female-determining

Y produces testis-determining factor (TDF)

CONCLUSION:

• crossing over between X and Y during meiosis occurs in pseudoautosomal region (PAR)……necessary for normal disjunction

• PAR homologous to region of X-chromosome

• non-recombining region of Y (NRY)unique to Y chromosome

• human Y chromosome contains gene SRY (sex-determining region Y) which makes TDF

• XY females deleted for SRY region are observed and XX males with TDF gene translocated to X chromosome

hemizygous gene

a gene present in only one copy in a diploid organism

e.g. any gene on the X or Y (NRY) chromosomein human males

Primary and Secondary Sex-RatioPrimary and Secondary Sex-Ratio

Y sperm more able to fertilize egg, or,better survival in reproductive tract

Y lacks most genes on X, any subvital/lethal genes uncovered in hemizygousmales, higher lethality

Explanationfor primary sex-ratio:

Primary 1 : 1.20 - 1.60Secondary 1 : 1.025 - 1.15Maturity 1 : 1Old Age 1 : <1

Autosomal genes are inherited in equal frequencies by both sexes

Aa x Aa

1AA : 2Aa : 1aa

(if allele a is recessive equal numbers of females and males should be affected)

Y-Chromosome Linkage in ManY-Chromosome Linkage in ManHolandric InheritanceHolandric Inheritance

Hairy Pinna

Y always inherited father to son

Gene found only on Y-chromosome

Inheritance of Sex (X)-Linked Inheritance of Sex (X)-Linked Traits Color BlindnessTraits Color Blindness

cc

CY

CYCY

CY

CC cY Cc cY Cc

CcCc Cc or CC

Cc or CC

Cc or CC

cY

= = colorblind

Color-blindness is a sex-linked recessive trait

• trait more common in males because of hemizygosity

Dosage Compensation in MammalsDosage Compensation in Mammals

Observation -- Trisomys-

XXX, nearly normalXXXY looks fairly normal21/21/21 Down’s quite abnormal13/13/13 Severely affected

Why can individuals tolerate additional X-chromosomesbut not additional autosomes?

How is X-chromosome gene expression controlled?

Dosage Compensation BackgroundDosage Compensation Background

1. Barr (1949) -- Observed chromatin bodies in the nerve cells of female cats. Somatic cells only.

2. Ohno -- Proposed Barr body is X-chromosome

3. The # of chromatin bodies is one less than the # of X-chromosomes. Restricted to somatic cells.

Interphase

X-chromosome inactivation in mammals

Cells of Cells of

XXX = XXXX = XY = XXY =

Dosage Compensation ExplainedDosage Compensation Explained

1. The chromatin body is an X-chromosome

2. One X-chromosome is inactivated - visible as a differentiallystained Barr body during interphase. Genes inactivated.

3. The inactive X can be either maternal or paternal in origin.

4. Inactive X-chromosome is late-replicating. It lags on the metaphase plate during mitosis.

5. X-inactivation in humans begins about 16 days into development.

6. Once an X-chromosome becomes inactive it will always be inactive in all cells derived from that cell.

Lyon Hypothesis (1962) (English Mouse Geneticist)

mosaic / chimera

- an individual composed of two or more genetically different cell types

Dosage Compensation (cont.)Dosage Compensation (cont.)

B

b

B

b

B B

B B BB b b b b

b b

Dosage Compensation Example Dosage Compensation Example Calico CatCalico Cat

Black BB BY

Calico Bb ----

Yellow bb bY

Exception: XXY Klinefelter male calico cat

Bridges Sex-Balance Theory Bridges Sex-Balance Theory Drosophila melanogasterDrosophila melanogaster

XW X+ Y

XW X+ XW Y

a) Crossed XW XW (x) X+ Y

The white eye gene in Drosophila was the first gene to be located on a chromosome.

Exceptional offspring occurred at low frequency1. White2. Wild type (sterile)

Wild Type White(red eye)

} Primary Exceptions

HypothesisHypothesis

XW XW (x) X+ Y [Primary non-disjunction]

XW XW X+ Y

XW XWX+ X+ OXW XWY OY

Metafemaledies

Sterile DiesFertile

Chromosomes of DrosophilaChromosomes of Drosophila

X

X

II

II

III

III

IV

IV

centromere

X & Y = Sex-chromosomes Autosomes

= XXAA II + III + IV= XYAA = 1 Set Autosomes (A)

Autosome = any chromosome that is not a sex-chromosome

Mutation of a third chromosome gene, C3G, leads to a high degree of non-disjunction.

Non-disjunction shown for X-chromosome and complete sets of autosomes.

XXXAAA (X) XYAA

Chromosome Segregation during Meiosis

X XX

A AA AA A

X XXXA XXAA XAA XXA

XXAA

XYAA

(Triploid )XXXAAA(Intersex)XXYAAA

(Intersex)XXAAA

(Meta )XYAAA

(Meta )XXXAA

XXYAA

XA

YA

CONCLUSIONS: Female and male determining factors onX-chromosome and autosomes

Y-chromosome carries male fertility genes

X:A ratio determines sex

XA XXAA XAA XXA

XXAA = 2/2 = 1 =XYAA = 1/2 = .5 =XXXAAA = 3/3 = 1 =XXXAA = 3/2 = 1.5 = MetaXYAAA = 1/3 = .33 = MetaXXYAA = 2/2 = 1 =XXAAA = 2/3 = .67 = IntersexXXYAAA = 2/3 = .67 = Intersex

.5 .67 1

Intersex

External Environment and Sex External Environment and Sex DeterminationDetermination

1. and have same chromosomes.

2. If young worm is raised from an isolated larva it becomes a female.

3. Drop larva in water with females. If larva comes in contact with female then larva turns into male and eventually migrates to female reproductive tract.

4. Possibly a hormone is secreted from the proboscis of female to initiate male sexual differentiation.

Bonellia Worm -- Marine Worm

Sex Determination in Turtles

• all males at 25oC

• all females at 30.5oC

Sex Determination in Alligators and Crocodiles

Alligators:

• all females at 31oC; all males at 33oC; all females at 35oC

• temperature affects levels of male and female sex hormones

Solving Pedigrees

5 basic types - autosomal recessive- autosomal dominant- sex-linked recessive- sex-linked dominant- Hollandric inheritance

1. Recessive characters often skip generations

2. Dominant characters are usually observed in every generation.

3. Autosomal characters are inherited equally by females and males.

4. Recessive sex-linked characters are inherited at a much higher frequency by males.

5. Y-linked characters are only inherited by males.

Hints:

- when determining inheritance of a rare mutation - if an individual marries into the family assume that the individual is homozygous for the wild-type allele (non-disease allele) unless there is evidence suggesting otherwise

- dominant mutations are usually lethal when homozygous; assume that individuals carrying dominant mutations are heterozygotes

- when determining the mode of inheritance in a pedigree be sure to rule out other possibilities

Duchenne Muscular Dystrophy : X - linked dominant inheritance

Rare autosomal recessive kidney disease

What is the probability that individuals 1 and 2 will have an affected child?