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SEX CHROMOSOME ABNORMALITIES
Sometimes during meiosis, the paired (MI) or daughter chromosomes
(MII) go to the same pole. This is described as "nondisjunction". If
nondisjunction involves the sex chromosomes, it results in eggs or sperm
with abnormal numbers of X and/or Y chromosomes.
In eggs, a single nondisjunction event leads to XX eggs and O (no X
chromosome) eggs.
Fertilization of an XX egg with an X sperm producesXXX (Triplo X)
females
Fertilization of an XX egg with a Y sperm produces XXY (Klinefelters)
males.
Fertilization of an O egg with an X sperm leads to
XO (Turners) females
Fertilization of an O egg with a Y sperm is lethal
Nondisjunction in males can lead to XX, XY, O and YY sperm.
Combining these with an X egg will produce the syndromes described
above plus XYY(Jacobs). Females with the karyotype 47; XXX are
fertile, tend to have XX and XY offspring, generally fall in the normal
range of IQ, and have no distinguishing characteristics. Many are
considered "shy" when young and may be delayed in social
development. There is great tendency for metal retardation when there
are 4, 5, or 6-X chromosomes present.
Overall frequency: about 1 in 4,000 live births.
Females with Turner syndrome (45; XO) are very short, sterile, and
have problems with "spatial" tests but otherwise tend to fall in the
normal IQ range. Development of secondary sex characteristics and
stature can be addressed by hormone therapy. Heart and kidney
problems are also common. Frequency: 1 in 2,000 to 1in 2,500 live
female births
Klinefelter males (47; XXY) tend to be tall, are infertile with very small
testes, generally lag in development of language skills, and often display
breast development at puberty. The latter is easily treated with
testosterone, but fertility is not restored. Frequency is estimated at 1 in
500 to 1 in 1,000 male births.
XYY males (Jacob syndrome) also tend to be taller than average and
have problems withacne but are fertile and have XY and XX children.
As a group they generally fall near the normal IQ range. Although there
is increased"risk" for XYY males to end up in penal institutions
(populations there are about 1 in 300 males compared to 1 in 1,000 at
birth) the vast majority are in the normal population. Early studies
suggesting "super" aggressive male behavior have not been borne out.
SEX DETERMINATION
Based on the previous information, it is clear that the primary
determinant of sex in humans is the presence or absence of the Y
chromosome, which is determined at fertilization; no Ys results in
female development; 1 Y, no matter how many Xs, produces male
development.
Special cells that can develop into gonads where meiosis takes place are
set aside very early in embryology. The tissue is called "ovotestes" since
it can develop into either ovaries
or testes.
Mullerian ducts are present that can develop into female internal
components.
Wollfian ducts that can develop into male components are present.
If a Y chromosome is present all the cells will display Hy antigen, a cell
surface protein coded by a gene on the Y chromosome.
After about 7 weeks, another Y encoded gene (called Tdf for testes
determining factor, or Sryf or sex-region of Y) is activated and directs
ovotestes to develop into testes.
Testes produce androgens, including testosterone, which induces
development of the Wollfian ducts and regression of the Mullerian
ducts.
After about 11 weeks, in the absence of a Y chromosome, female
development is initiated with the conversion of the ovotestes into
ovaries, regression of Wollfian ducts, and development of Mullerian
ducts.
Hormonal changes at puberty further advance sexual development.
Gonadotropic hormones (FSH and LH) from the pituitary, via a signal
from the hypothalamus, start monthly cycle of egg maturation and
release in females which increases estrogen, which decreases FSH and
LH, etc. In males, trace levels of the same hormones lead to induction of
secondary sex characteristics, (beards, voice, etc.). Adrenal hormones
lead to puberty changes in females. Very few if any of the genes needed
for sexual development/identity are on the sex chromosomes. After
birth, it becomes difficult to separate genetic effects from non-genetic
effects since males and females often are treated with "different
expectations".
As would be predicted since many hormones are involved, each of
which is produced via biosynthetic pathways, many different mutations
can affect normal sexual development. The bulk of the genes are not
sex-linked or holandric, but are located on somatic chromosomes.
Examples of genetic defects that alter sex development include:
Tfm, an X-linked gene that codes for testosterone receptors. Females
whoare XTfmXtfmare normal. Their XtfmY progeny, expected to be males,
developinto sterile females (condition is called testicular feminization or
completeandrogen insensitivity). Although the ovotestes become testes
andproduce testosterone, it has no effect, so the outward and
mentaldevelopment becomes female. Unfortunately, the Mullerian
ductsdisintegrate so there is no chance of fertility, and the undescended
testesshould be removed after puberty to diminish the risk of cancer.
In guevodoces, infants are classified as female at birth based on external
genitalia. At puberty they "convert" to fully functional males; which
some, but not all have claimed to be all along.
When hormone therapy or surgery is used, the best bet is to make the
appearance match the "brain-sex" of the individual.