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Phenotypic sex is determined by a sequential process that involves
the establishment of chromosomal and genetic sex in the zygote at
conception, gonadogenesis and the determination of gonadal sex (sex determination),
and sexual differentiation of the genital tract and external genitalia
as programmed by gonadal sex.1 Divergent differentiation
from the sex chromosome constitution is possible at each level of
sexual organization. Table 538-1 considers
the hierarchal ontogeny of sex from chromosomal sex to gender identity.
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Recent advances allow more accurate prenatal diagnosis of sex.
This is of particular importance when embryo gender determination
is desired for gender determinations of X-linked disorders. Despite
preimplantation sex determination, in about 1% of cases
of mistakes occur in preimplantation sex assignment. Ultrasound or amniocentesis
allows sex determination in the second trimester, and chorionic
villus sampling allows determination and molecular analysis of X-linked
genetic disorders during the first trimester, but it is associated
with a risk of fetal loss. Newer techniques that measure maternal
plasma cell-free fetal nucleic acids (DNA and RNA), such as sex
determining region (SRY) gene amplification, allow reliable determination
of sex early in the first trimester.2
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In placental mammals, the male is the heterogametic sex, XY,
and the female is homogametic, XX. The Y chromosome functions as
a dominant male determinant. The XX and XY are the chromosomal basis
of sex determination.1,3-5 The sex chromosomes
and the autosomes harbor genes that regulate sex determination and,
as a consequence, gonadogenesis. Although the presence of only a
single X chromosome (as in 45,X gonadal dysgenesis) can lead to
the beginning of ovarian organogenesis, with rare exceptions 2 X
chromosomes are required for survival of oocytes in utero and the
development of a normal ovary at birth. Two X chromosomes (in the
absence of a Y chromosome or translocation of its testis-determining
gene to an X-chromosome) lead to ovarian differentiation.
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Sex Chromatin
Pattern (Barr Body)
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The 2 X chromosomes in female diploid somatic cells exhibit striking
morphologic and functional differences. One X chromosome is in a
highly condensed (heteropyknotic) state in interphase and is visible as
sex chromatin (Barr body).6 It completes DNA synthesis
later than any other chromosome, and the action of genes located
on the precociously condensed segments is suppressed (silent X)
by transcriptional inactivation.7-9 The other X
chromosome, the single X chromosome in male somatic cells, is in
a highly extended (isopyknotic) state during interphase. It completes
DNA replication with most of the complement and is genetically active.
This discordant behavior of the 2 homologous X ...