Sex Diff Substrates: Autosomal Contributions

Teresa Binstock binstoct at essex.hsc.colorado.edu
Tue Aug 8 13:03:06 EST 1995


The following discussion explores the concept of how autosomal genes
might contribute to sexual orientation and/or to gender orientation.     
8.8.95


             AN AUTOSOMAL GENE WITH SEX-SPECIFIC EXPRESSION:

The acronym PDHA2 refers to one of two variants of the E1-alpha subunit
of pyruvate dehydrogenase, an enzyme involved in aerobic metabolism. In
humans, PHHA1 (the other variant) occurs on the X chromosome within
Xp22.1-22.2; PDHA2 occurs on chromosome 4; and PDHA2 expression is
testis specific (Fitzgerald et al).

COMMENTARY:

Because testes are generally (though not always) found in X,Y males,
PDHA2 is an example of an autosomal gene that is expressed only in
males. This suggests that other autosomal genes may be expressed only in
males. 

If male-specific expression of certain autosomal genes (not necessarily
PDHA2) occurs in the male brain, then dysregulations of those genes
might contribute to feelings and behaviors that are other than X,Y-male
typical. 

BOTTOM LINE: The search for genes that may contribute to sexual- and
gender-orientation ought not be conceived as "limited to X and Y
chromosomes". 

                                  *****
              Fitzgerald J et al: Genomics 18.636-42 1993.
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                                  *****
                      Commentary & Addenda Portions
                              Copyright 1995
                                  *****
                     Teresa C. Binstock, Researcher
                 Developmental & Behavioral Neuroanatomy
                                  *****

ADDENDA:

1. Retinitis pigmentosa (RP) provides a clear example of many different
genes each sufficiently capable of inducing similar phenotype (ie
retinitis pigmentosa). Note that RP genes have been identified on
autosomes and on the X-chromosome. That similar phenotype can be induced
from genes on various chromosomes may well be applicable in searching
for biological substrates of sexual and gender orientation and
variations thereof.
     Sample article: X-linked dominant cone-rod degeneration:
     linkage mapping of a new locus for retinitis pigmentosa (RP15)
     to Xp22.13-p22.11. 
          McGuire RE et al Am J Hum Genet 57.87-94 1995.

2. Another factor that is not mentioned in most sex differentiation
research articles is that autosomal male and female chromosomes often
have different rates of recombination. To some extent, these differing
rates correspond not only to centiMorgan length but also to actual
physical length differences. (Principles of Medical Genetics; Gelehrter
& Collins, 1990; p204) As we explore physiological bases of sex
differences we ought ask questions like:
a. What causes male and female autosomes to have different lengths? 
b. When are these differences initiated?
c. In what direction are these length differences in XX males and in 
   XY females?
d. Do these differing lengths affect intracellular and intercellular 
   events?
e. Given whatever causes these male/female differences in chromosomes    
   length, is that cause also doing other things to intra- and inter-   
   cellular processing?
     Sample article: A new dinucleotide repeat polymorphism at the
     telomere of chromosome 21q reveals a significant difference
     between male and female rates of recombination.
          Blouin JL et al Am J Hum Genet 57.388-94 1995.

3. An article made available today in Colorado specifically explores Y
chromosome versus autosomal contributions to aggressive behavior. This
kind of focus may be applicable with regard to sexual- and gender-
orientation and to other gender-typical behaviors, ie researchers ought
consider autosomal genes as well as XX and XY genes. 
     Sample article: Autosomal and Y chromosomal effects on the
     stereotyped response to apomorphine in wild house mice.
          Sluyter F et al Pharmacol Biochem Behav 52.1.17-22 1995

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