Flashcards in Sex Determination & XY Chr. Disorders (Manchester) Deck (45)
What are the advantages of sexual reproduction? (keep it clean now...)
1. Diploidy - protects against effects of mutation. you have a back-up gene
2. Random chromosomal assortment - increases variation
3. Recombination - new gene combos; speciation _protection_
4. Imprinting - regulates gene expression
What are the features / advantages of sexual dimorphism of a species?
1. Division of Labor - particularly w.r.t. reproduction
3. Sexually dependent selection - females (XX) have the advantage
Why do females (XX) have the selection advantage over males?
The females "store" the X chromosomes and select the males (only one X). Can select a mate for a specific trait and influence the genotypes that are kept - particularly the traits on the X chromosome.
What are Dr. Manchester's levels of sex?
2. Gonadal development
3. Anatomic develoment
4. Genital development
In mammals, the embryo is preprogramed to produce a _____(M or F)______ phenotype unless _______________.
Female phenotype is default
unless specific sequences on the Y chromosome are present AND expressed.
Which embryonic structures form the duct systems in males vs. females?
mesonephric ducts regress
paramesonephric ducts ---> female duct system (Fallopian tube etc.)
Y chr. present; SRY/TDF expressed
mesonephric ducts --> male duct system (from testes on up)
Where is the SRY gene located?
SRY (sex-determining region on Y) is located on the Y chromosome.
In particular, on the short arm of Y (Yp) near but not in the pseudo-autosomal region on Yp.
What is the pseudoautosomal region on the X and Y chr's?
Regions where recombination between X & Y can occur during meiosis.
What other genes are on the Y chromosome (as mentioned in lecture)?
2. DAZ gene - expressed only in pre-meiotic germ cells; important for spermatogenesis
3. USP9Y gene - "ubiquitin specific peptidase 9 on Y) - important for sperm production
4. AZFa, b and c - azoospermia factor
5. a lot of satellite DNA on the long arm
What is a Barr body?
The inactivated X chromosome in a female cell
Females are mosaic. Half their cells express one X chr, the other half will express the other X chr.
Barr body is visibly present in interphase.
What gene is in charge of X-inactivation?
Briefly explain how X-inactivation occurs.
is a noncoding RNA that associates with the inactive X
promotes DNA methylation (silencing) and histone protein modifications
How much of an deactivated X chromosome is actually inactive?
What are some consequences of this?
85-90% in inactive.
the other 10-15% 'excapes' inactivation and is in fact expressed.
Females thus express more genes than males.
Helps to explain Turner Syndrome. Even though an X is "inactive" in every female cell, a few genes are still on and are necessary for normal development.
Explain how X-inactivation may not be random.
1. Abnormal X chromosome: the normal one stays active. likely due to death of the cells with the abnormal one active.
2. Balanced X;autosome translocation: ** the normal X is inactivated *** possibly selecting agains inactivation of autosomal genes.
3. Unbalanced X;autosome translocation: inactivation of the abnormal der(X) chromosome.
How might nonrandom X inactivation be deleterious even if the most "normal" X is still active?
If the normal X chromosome carries an X-linked recessive mutation, it is no longer protected by the other X carrying the dominant (non-mutant) allele.
EX: Duchenne Muscular Dystrophy. X-linked recessive; rare cases in females are due to X-inactivation favoring the disease carrying X chr.
Do you remember where the primordial germ cells come from?
The yolk sack! The migrate into the genital ridge
What two genes are responsible for formation of gonads right as the germ cells are migrating into the genital ridge?
SF1 - steriodogenic factor 1
WT - Wilms tumor gene- tumor supressor gene; urogenital development in males
mutations in these genes result in ovaries even in an XY individual
What genes determine if you get ovaries or testes?
SRY / TDF
What do SOX9 and DAX1 do?
SOX9 gene -> SOX9 protein --> interacts with MIF (mullerian inhibiting factor). crucial for normal male reproductive machinery.
DAX1 gene = dosage sensitive sex reversal, adrenal hypoplasia critical region on X chromosome (woah) - anti-testes gene, antagonist of SRY
SRY gene mainly acts on what gene?
Two DAX genes in males does what?
two DAX in females leads to becoming female. (dosage sensitive!!)
What does MIF do?
MIF produces active regression of Müllerian ducts.
Otherwise the Müllerian ducts become the Fallopian tubes etc.
What is the prostatic utricle?
remnant of Müllerian duct in males. is estrogen responsive so important in prostate cancer.
From what structure does the uterus form?
Development of male external genitalia is __________ dependent.
What example was given in lecture regarding brain sexual dimorphism?
language processing in the brain
female: both sides more
male: one side more
What cells produce MIF in males?
What do the leydig cells do in males?
What does steroid 5-alpha-reductase do?
What does 5-alpha-reductase deficiency do in 46-XY individuals?
Normally stimulates external genitalia developent.
5-alpha-reductase deficiency (autosomal recessive)results in failure of end organs to activate testosterone to dihydortestosterone (DHT)
*incomplete phallic development
*severe hypospadias (pseudovaginal perineal hypospadias)
Describe leydig cell hypoplasia
lack of testosterone production --> male pseudohermaphriditism
defect is mutation in LHR gene (luteinizing hormone receptor)