Determination of Sex Flashcards
What are the advantages of sexual reproduction?
it speeds evolution and contributes to survival of species by increasing genetic variability
it also protects and preserves species
Describe X inactivation
Cells from normal females inactivate one X chromosome.
Random, so females are mosaic (half paternal X, half maternal X)
How? DNA methylation and modifications of histone proteins that depend on expression of the XIST gene on the inactive X.
XIST gene encodes noncoding RNA, which is expressed in cell nuclei where it associates in cis (i.e. with the inactive X) as part of an XIST RNA/Barr body complex
___% of the genes on X escape inactivation. Many are located on the _______________.
10-15%
Many are located on Xp. The pseudoautosomal region of Xp shares enough homology with Y to pair and recombine with it during meiosis.
What is non-random X inactivation?
When an X chromosome is abnormal or there is an X;autosome translocation.
Cytogenetic analysis looking for this translocation is indicated when a female presents with an X-linked recessive phenotype.
In the absence of cytogenetic abnormalities, nonrandom X inactivation can be diagnosed by analyzing the methylation pattern of highly polymorphic X chromosomal loci (e.g. gene for the androgen receptor, AR, Xq11-12).
What is SRY’s role in sex determination?
If present, gonads develop into testes. In it’s absence, ovaries form.
What non-SRY mutations can lead to sex reversal?
Mutations at 3 autosomal loci on chromosomes 9, 11, and 17
What other genes are important?
WT (11p13): directs differentiation of the mesonephros and genital ridge
SOX9 (17q): makes SOX protein which interacts with SRY & DAX1
SRY + SF1 bind to SOX9 enhancer
SF1 and SRY upregulate SOX9, then SF1 & SOX9 bind to an enhancer and upregulate itself
Loss of SF1 leads to..
adrenal hypoplasia and gonadal agenesis
Duplication of DAX1 in males leads to
development of ovaries (DSSR)
What are the 2 stages of germ cell development
sexually independent pregonadal (migrate from yolk sac to gonads) gonadal dependent (maturation)
Male genital sex is regulated by…
hormones produced by differentiated testes (absence of this –> female development)
Normal testes contain 2 non-germ cells
Sertoli (produce MIF aka AMH aka MIS)
Leydig (produce testosterone via pit stim)
What does MIF do?
prevents formation of mullerian ducts (fallopian tubes, uterus, upper vag)
Testosterone stimulates…
development of Wolffian duct into epididymal duct & DD. No test = degeneration of these
Also causes indeterminate female genitalia to become penis & scrot. No test = penis becomes clit, vag stays open
What does the genital tubercle become?
Male: penis (glans & shaft)
Female: clitoris (glans & shaft)
