3. SEX DETERMINATION AND SEX CHROMOSOMES

two X

chromosomes

The human females have

one X and one Y

chromosome

The human male has

Genetic sex

established at the time of fertilization and

is dependent on whether an X- or Y-bearing

sperm fertilizes the X-bearing egg

Gonadal sex

the type of gonads that develop, is

determined by the sex chromosome

complement (XX or XY) sex-determining

genes.

Before the seventh week

of embryonic

life, the gonads of both sexes appear

identical.

testis

under the influence of the Y

chromosome, the immature gonad

becomes a

Pseudoautosomal Regions

Distal region of the p arms of the X and

Y chromosomes contains highly similar

DNA sequences

pseudoautosomal region of

PAR1

Resembles the crossing-over in

autosomes, hence it is termed

PAR2

a region of homology is at the

distal ends of Xq and Yq, which has

been observed to associate during male

meiosis, with proven recombination

events.

PAR1

is 2.6 Mb and contains at least 24

genes

PAR2

is only 320 kb and

has 4 genes

Lyon hypothesis

The X inactivation is also termed, the

Dr.

Mary Lyon

Lyon hypothesis after its proponent

Mary Lyon

In 1961, the single active X chromosome

mechanism of X-dosage compensation in

mammals was developed by

Barr body

when a female’s X

chromosome becomes inactivated, it is

converted into a

Susumo Ohno

was the first to suggest

that the Barr body arises from one of the

two X chromosomes

BARR BODIES

Inactivated X chromosome

BARR BODIES

Provides a mechanism for dosage

compensation

BARR BODIES

If one of the two X chromosomes is

inactive in the cells of females the dosage

of genetic information that can be

expressed in males and females is

equivalent.

XIST

(X-inactive-specific transcript)

A gene that controls X inactivation is

X-inactivation center

(XIC) at band Xq13

X- CHROMOSOME

INACTIVATION It is located at the

XIST

encodes a large molecule of RNA

(XIST RNA)

XIST RNA

accumulates along the X

chromosome containing the active XIST

gene and proceeds to inactivate all (or

almost all) of other genes on that

chromosome

Pseudoautosomal regions

at the distal p

and q arm, PAR1 and PAR2

Heterochromatic region

on the q arm

Male Specific Region of the Y (MSY)

located between PAR1 and PAR2

78

__ protein-coding genes

27

__ distinct proteins

12

__ of the MSY genes are

expressed in many organs

11

__  MSY

genes are expressed

predominantly in the testes

Azoospermia factor (AZF)

A gene controlling spermatogenesis

Tiepolo and Zuffardi

A gene controlling spermatogenesis, was

first proposed by

euchromatic Yq11

region

Azoospermia factor (AZF) mapped to the distal part of the

Testis-determining factor (TDF)

Leads to differentiation of the indifferent

gonads into testes

short arm of

the Y chromosome

Testis-determining factor (TDF) located on the

Gene SRY (sex-determining region Y)

It is located on the short arm of the Y at

band p11.3 in the MSY region

short arm of the Y at

band p11.3 in the MSY region

Gene SRY (sex-determining region Y) It is located on the

Mosaicism

is more common for sex

chromosome abnormalities than

autosomal abnormalities

TURNER SYNDROME

45,X

TURNER SYNDROME

One of the most common chromosome

abnormalities in spontaneous abortions

TURNER SYNDROME

75% of patients with 45,X, the X

chromosome is maternal in origin.

KLINEFELTER SYNDROME

First sex chromosome disorder to be

described and its cytogenetic cause

identified

KLINEFELTER SYNDROME

47,XXY

KLINEFELTER SYNDROME

Most common cause of hypogonadism

and infertility in males

47,XYY

One in 800–1,000 males has an extra Y

chromosome

47,XYY

This arises through nondisjunction at

paternal meiosis II.

Turner syndrome

Isochromosome Xq commonly found in

patients with

X CHROMOSOME

Involved in translocations, bot balanced

and unbalanced

Isochromosome X

consisting of two

copies of the long arm (missing all or most of the

short arm)

Y CHROMOSOME

Lead to deletion of the proximal long arm

might be associated with azoospermia,

infertility, and short stature

Marker chromosomes 

are important to

detect due to the risk of gonadoblastoma

in females with Turner syndrome.

FISH probes and chromosome

microarray

identify marker Y

chromosomes.