Sex determination and Sex chromosomes - WEEK 5

• 46 total chromosomes (23 pairs)

  • 22 pairs of autosomes

  • 1 pairs of sex chromosomes

How many chromosomes does a normal person have?

• XX — females

• XY — males

What are the pairs of female and male sex chromosomes?

1. Lyon hypothesis

2. Dr. Mary Lyon

3. 1961

What is the other name for X inactivation hypothesis? When was it developed?

X inactivation or Lyon Hypothesis

States that 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.

X inactivation or Lyon Hypothesis

It is the single active X chromosome mechanism of X-dosage compensation in mammals was developed

1. female’s X chromosome

2. Barr body

Based on the X inactivation:

In a given cell, what becomes inactivated? what does it converted into?

All defscendants of the cell will be inactivated as well

What happens after a female’s X chromosome becomes inactivated?

The dosage of genetic information that can be expressed in males and females is equivalent

What happens if one of the two X chromosomes of a female becomes inactivated?

Barr bodies

It a sex chromatin body, and is the inactivated X chromosome

Susumo Ohno

Who was the first to suggest that the Barr body arises from one of the two X chromosomes

1. XIST —— X-inactive-specific transcript

2. XIC —— X-inactivation center

   1. band Xq 13

1. What gene controls the X inactivation?

2. “This” gene is located where? at what band?

inactive X

Only the _________ expresses the XIST

RNA (XIST RNA)

What molecule encodes the XIST (X-inactive-specific transcript)

XIST RNA

Barr bodies are inactive chromosomes that is painted with ____________

• p arm — short

• q arm — long

What is the short and long arm of the chromosome

• Pseudo-autosomal regions (PAR1 & 2) ——- at the distal (end) of p and q arm

• Heterochromatic region —— on the q arm

• Male Specific Region of the Y (MSY) ——- between PAR1 and PAR2

What are the different regions of the Y chromosome?

• 78 protein-coding genes

• 27 distinct proteins

The Male Specific Region of the Y (MSY) has:

• ____ protein-coding genes that encode _____ distinct proteins

• 12 of the MSY genes ——— many organs throughout the body

• 11 of the MSY genes ——— testes

• Where is the 12 genes of MSY expressed?

• What about 11 MSY genes?

Azoospermia factor (AZF)

This is a gene controlling spermatogenesis and is mapped to the distal part of the euchromatic Yq11 region

Tiepolo and Zuffardi in 1976

They first proposed the Azoospermia factor (AZF)

Testis-determining factor (TDF)

This gene leads to differentiation of the indifferent gonads into testes, locates on the short arm of the Y chromosome

Gene SRY (sex-determining region Y)

It is located on the short arm of the Y at band p11.3 in the MSY region

Numerical (Aneuploidy)

Sex Chromosome Abnormality:

NUMERICAL vs STRUCTURAL ——— which is more common?

Mosaicism

Sex Chromosome Abnormality:

MOSAICISM vs AUTOSOMAL ———- which is more common?

Turner Syndrome

45, X

1 in 2,500 live-born females

Turner Syndrome (45,X) occurs in approximately ______________ live-born females

Turner Syndrome (45,X)

One of the most common chromosome abnormalities in spontaneous abortions

X chromosome maternal in origin

What chromosome is maternal in origin of among 75% of patients with Turner Syndrome (45,X)

Turner Syndrome (45,X)

What abnormality is this?

• decreased mean birth weight

• posteriorly rotated ears

• neck webbing

• edema of hands and feet

Turner Syndrome

What abnormality is this?

• short stature and ovarian failure

• posteriorly rotated ears

• low posterior hairline

• webbed neck

• short fourth metacarpals

• cubitus valgus

Turner Syndrome

Patients with this abnormality may develop problems with visual-spatial skills, working memory, executive functions, and social skills can occur

Turner Syndrome (45,X)

Infants with this abnormality can have feeding problems and developmental delay.

Trisomy X

47, XXX

Trisomy X (47,XXX)

This abnormality is the most frequent sex chromosome disorder present at birth in females

superfemale

Trisomy X (47,XXX) was termed ___________ but gives a misconception of the syndrome and is no longer in use

Trisomy X (47, XXX)

What abnormality is this?

no recognizable syndrome in females compared to 45,X

• Pubertal development is normal

• normal fertility

• small number have ovarian dysfunction and premature ovarian insufficiency sometimes associated with autoimmune thyroid

Trisomy X (47,XXX)

Female patients with this abnormality have normal intelligence, but most have lower IQs than their siblings.

Klinefelter Syndrome

47, XXY

Klinefelter Syndrome (47.XXY)

This is first sex chromosome disorder to be described and its cytogenetic cause identified

Klinefelter Syndrome (47,XXY)

This abnormality is the most common cause of hypogonadism and infertility in males

Klinefelter Syndrome (47, XXY)

What abnormality is this:

• Taller than average stature

• Eunuchoid build with long limbs and pear-shaped hips

• Testicular and penile size is usually small during childhood

• Gynecomastia occurs in up to 50% of males during adolescence

Klinefelter Syndrome (47, XXY)

Boys with this abnormality have been reported to have decreased muscle tone during infancy, delayed speech and language skills, and an increased incidence of reading disability and dyslexia

Barr Murray

Discovered the Barr body