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Does having a Ychromosome makesomeone a man?

Classification: FA Q

A lot of unintended harmhappens when people

assume a Y chromosomemakes a person a boy or aman and the lack of a Ychromosome makes aperson a girl or a woman.For example, onephysician educator on ourMedica l Adv isor y Board  had the challengingexperience of trying tocalm a 23-year-old patientwho had just been told bya resident that she was “really a man” because the

resident had diagnosedthe patient as having a Ychromosome and completeandrogen insens i t i v i t y  s y nd r om e (CAIS).

It is true that in typicalmale development, theSRY gene on the tip of theY chromosome helps tosend the embryo down themasculine pathway. Butmore than the SRY isneeded for sexdetermination anddifferentiation; forexample, women withCAIS have the SRY genebut lack androgenreceptors. In terms of hormone effects on theirbodies (including theirbrains), women with CAIShave had much less “masculinization” than theaverage 46,XX womanbecause their cells do notrespond to androgens.

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Moreover, the SRY genecan be translocated ontoan X chromosome (so thata 46,XX person maydevelop along a typicalmasculine pathway), andthere are dozens of geneson chromosomes otherthan the X and the Y thatcontribute to sexual

differentiation. Andbeyond the genes, aperson’s sex developmentcan be significantlyinfluenced byenvironmental factors(including the maternaluterine environment inwhich the fetusdeveloped).

So it is simply incorrect tothink that you can tell aperson’s sex just looking

at whether he or she has aY chromosome.

Want to know more? Thefollowing comes fromISNA’s Medical AdvisoryBoard member Dr.Charmian Quigley:

SRY, discovered in 1989,is a small gene located atthe tip of the short arm of the Y chromosome. So

what does it do? Actually,like all genes, it doesnothing except to act as ablueprint for a protein. Inthis case, the protein of the same name doesfunky things to DNA, likebending it and unwindingthe 2 strands, so thatother proteins can get inand attach themselves toother genes that are thenturned on. So how did thisgene get its reputation(and its name) as the “sexdetermining” gene?

As is pretty common in theworld of genetics, this wasbecause of some errantmice. Researchers inEngland took a laboratory-made copy of this geneand inserted it artificiallyinto a female (XX) mouseembryo at a very earlystage of development. Themouse was “converted” 

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from female to male, sothe gene must have beenresponsible – right? Well,maybe not. A few yearslater, a similar gene wasfound on humanchromosome 17. When theimportant part of this genewas inserted into a femalemouse embryo, the samething happened. Voila! Amale.

So now we have 2 genesthat can turn a female intoa male, and one of them isnot located on the Ychromosome! How canthat be? It turns out thatSRY is probably just afacilitator that allows amore critical gene (orgenes) to function, byblocking the action of another opposing factor.

Can the magic of geneticsdo the opposite – turn amale into a female?Indeed it can. A gene onthe X chromosome (thechromosome one typicallyassociates with “femaleness”) called DAX1when present in doublecopy in a male (XY)mouse, turns it into afemale.

So now we have genes on

the Y that can turnfemales with XXchromosomes into malesand genes on the X thatcan turn males with XYchromosomes intofemales… wow! Malenessand femaleness are NOTdetermined by having an Xor a Y, since switching acouple of genes aroundcan turn things upsidedown.

In fact, there’s a whole lot

more to maleness andfemaleness than X or Ychromosomes. About 1 in20,000 men has no Ychromosome, insteadhaving 2 Xs. This meansthat in the United Statesthere are about 7,500 menwithout a Y chromosome.The equivalent situation -females who have XYinstead of XXchromosomes - can occurfor a variety of reasons

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and overall is similar infrequency.

For these 15,000 or moreindividuals in the US (andwho knows how manyworldwide), theirchromosomes areirrelevant. It is the totalcomplement of their genesalong with their life

experiences (physical,mental, social) that makesthem who they are (or anyof us, for that matter).The last time I counted,there were at least 30genes that have beenfound to have importantroles in the developmentof sex in either humans ormice. Of these 30 or sogenes 3 are located on theX chromosome, 1 on the Ychromosome and the rest

are on otherchromosomes, calledautosomes (onchromosomes 1, 2, 3, 4,7, 8, 9, 10, 11, 12, 17,19).

In light of this, sex shouldbe considered not aproduct of ourchromosomes, but rather,a product of our totalgenetic makeup, and of the functions of these

genes during development.

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nex t

u p

Is a person who is intersexa hermaphrodite?Is intersex the same as"ambiguous genitalia"?

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