Guevedoce

Spanish for "testicles at 12"

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Guevedoce

#1  Postby aban57 » Nov 08, 2017 8:56 am

I find this medical case to be fascinating. I sometimes use it when people have trouble understanding how a man can "feel" like a woman, or vice versa.

When you are conceived you normally have a pair of X chromosomes if you are to become a girl and a set of XY chromosomes if you are destined to be male.
For the first weeks of life in womb you are neither, though in both sexes nipples start to grow.
Then, around eight weeks after conception, the sex hormones kick in. If you're genetically male the Y chromosome instructs your gonads to become testicles and sends testosterone to a structure called the tubercle, where it is converted into a more potent hormone called dihydro-testosterone This in turn transforms the tubercle into a penis. If you're female and you don't make dihydro-testosterone then your tubercle becomes a clitoris.
When Imperato-McGinley investigated the Guevedoces she discovered the reason they don't have male genitalia when they are born is because they are deficient in an enzyme called 5-alpha-reductase, which normally converts testosterone into dihydro-testosterone.
This deficiency seems to be a genetic condition, quite common in this part of the Dominican Republic, but vanishingly rare elsewhere. So the boys, despite having an XY chromosome, appear female when they are born. At puberty, like other boys, they get a second surge of testosterone. This time the body does respond and they sprout muscles, testes and a penis.


From Wikipedia :
5α-Reductase deficiency (5-ARD) is an autosomal recessive intersex condition caused by a mutation of the 5α reductase type II gene.


The condition is extremely rare, with areas of greater incidence known in regions of the Dominican Republic, Papua New Guinea, and Turkey.
The cases of the condition reported in the Dominican Republic are of greatest interest due to its prevalence in the small remote village of Las Salinas, where 12 out of 13 families had one or more male family members that carried the genetic mutation, though not all the carriers of the mutation were affected. The overall incidence for the village was 1 in every 90 males were affected carriers, the remainder of the village genetic males were either non-carriers or non-affected carriers.
It is thought that either a founder effect or a bottleneck effect (the villagers are interrelated and may have inherited the mutation from the same individual), in conjunction with a lack of geneflow (genes from outsiders) in the isolated geographic location of Las Salinas allowed the mutation to become amplified in the village.


I'm wondering why " not all the carriers of the mutation were affected".
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Re: Guevedoce

#2  Postby Calilasseia » Nov 08, 2017 3:39 pm

The answer is in that first Wikipedia paragraph you quoted - it's an autosomal recessive condition. Individuals only manifest the condition if both copies of the mutant gene are inherited.

Let D represent the normal 5α-reductase gene, and d represent the defective version of the gene. individuals inherit two genes, one from the mother, one from the father.

If the individual inherits a D from his mother, and a D from his father, his genotype is DD, and he is unaffected by the condition.

If the individual inherits a D from his mother, and a d from his father, his genotype is Dd, and he is likewise unaffected by the condition. The working D gene is dominant, and preferentially expressed, therefore he produces a working version of the enzyme, and the DHT pathway operates as normal.

If the individual inherits a D from his mother, and a d from his father, his genotype is dD, and he is likewise unaffected by the condition. The working D gene is dominant, and preferentially expressed, therefore he produces a working version of the enzyme, and the DHT pathway operates as normal.

If the individual inherits a d from his mother, and a d from his father, his genotype is dd, and he is affected by the condition. None of his copies of the 5α-reductase gene are working, so the DHT pathway is not triggered as normal.
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Re: Guevedoce

#3  Postby aban57 » Nov 08, 2017 3:44 pm

Weird, I thought I read somewhere that the faulty gene was on the Y chromosome.
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Re: Guevedoce

#4  Postby Calilasseia » Nov 08, 2017 4:03 pm

No. "Autosomal" means "on chromosomes other than the X any Y chromosomes".

For example, Factor VIII haemophilia is not autosomal, because, bizarrely, the gene for clotting factor VIII resides on the X chromosome (at least in humans). Consequently, factor VIII haemophilia is a sex-linked recessive disease. Women generally don't suffer from this, as they inherit two X chromosomes, and even if one of them carries a defective factor VIII gene, the other usually carries the normal gene, and this is dominantly expressed. However, women inheriting this combination become carriers of the condition.

Men, on the other hand, inherit an X and a Y chromsosome, and there isn't a copy of the factor VIII gene on the Y chromosome. So a man inheriting an X chromosome with a defective factor VIII gene is stuffed, because unlike a woman, he won't have a partner gene overriding the defective one. That's why factor VII haemophilia is seen most frequently in men. Only on the very rare occasion that a woman inherits TWO defective factor VIII genes, one from each parent, will a woman manifest factor VIII haemophilia.

Autosomal chromosomes, of course, are always inherited in pairs, regardless of sex. So there's usually no sex linkage between autosomal recessive genetic disorders, though in some cases, some rather intricate mechanisms can come into play to create a sex bias.

Matters become somewhat more complicated once incomplete dominance or codominance plays a role.
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Re: Guevedoce

#5  Postby aban57 » Nov 08, 2017 5:55 pm

Thanks :)
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