Dermatoglyphics & X-Inactivation Mosaicism: Neuronal Significance

Teresa Binstock binstoct at essex.hsc.colorado.edu
Wed Jun 28 16:56:57 EST 1995


DERMATOGLYPHICS & X-INACTIVATION MOSAICISM: NEURONAL, GENETIC SIGNIFICANCE

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                           Teresa C. Binstock

Minor physical anomalies (MPAs) and various neuropschiatric traits have
long been perceived as showing "soft" correlations. This has been
attributed to the fact that epidermal features and the central nervous
system arise from the same general area of the embryonic ectoderm; thus a
developmental dysregulation that affects the ectoderm may well induce MPAs
as well as "minor" lesions of the cns in ways that affect behavior. 

In a recent posting I called attention to X-inactivation mosaicisms in the
skin of mice, hamsters, calico cats and humans and to a recent article
documenting X-inactivation mosaicisms in murine brains (for cites, see
NeuroPsychological Traits-Diversity: X-Inactivation In-Brain Mosaicisms;
TC Binstock 1995). In that Net-article a conditional hypothesis was
offered:
     If such X-inactivation mosaicism exists in the brains of human
     females, then that mosaicism would help account for pleiotropic
     scores among groups of females having X-linked mutations that
     affect the cns and/or brain and/or physical anomalies.

Since then, a newly published article appears to provide a preliminary way
to examine several aspects of genetics and X-inactivation as observable in
dermatoglyphics of mice with a cns-related gene "knocked out".

The new article is:
         Dermatoglyphics on Volar Skin of Mice: The Normal Pattern
                  The Anatomical Record 242.2.225-32 1995
                           Tsugane M & Yasuda M

And we shall consider mice in whom FMR-1, the fragile X syndrome gene, has
been genetically "knocked out":
    Fmr1 knockout mice: a model to study fragile X mental retardation.
                           Cell 78.1.23-33 1994
                    Dutch-Belgian Fragile X Consortium

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                     AN EXPERIMENT WITH RAMIFICATIONS

A relatively "easy" experiment would involve comparing dermatoglyphic
patterns on groups of mice genetically identical except for the FMR-1
knockout.

THREE FACTORS ARE CONSIDERED:

I. BASIC QUESTIONS:  Female X-inactivation patterns are known to be
mosaical in the skin of humans, mice, rats, hamsters, and calico cats.
     In response to the above cited Internet article A. Holtzman (personal
communication) asked about the effects of X-inactivation mosaicisms upon
dermatoglyphic patterns -- perhaps as induced by skin-related mutations on
the X chromosome -- a notion from which many considerations ensue...
A.   Do mice show X-inactivation mosaicism in the skin of their paws? 
B.   Can X-activation ratios be determined for various areas of murine
skin? C.  Would different skin areas of the same individual mouse have
different      activation ratios? 
D.   If so, would this kind of X-inactivation mosaicism extend to murine
     dermatoglyphics?
E.   Does the skin of human fraX-females show X-inactivation mosaicism re:
     FMR-1 and activation ratios per various skin areas per person?
F.   If so, would this kind of X-inactivation mosaicism extend to
     human female dermatoglyphics?


II. FRAGILE X AS AN EXAMPLE:  Answers to the above questions about skin
and dermatoglyphics have ramifications for interpreting data when
dermatoglyphics are studied in large numbers of non-fraX and fraX females.

A.   If there is X-inactivation mosaicism in fingers as there is in
     other parts of human skin, then some fingers of some individual
     fraX-females would show the effects of mutated FMR-1, and other
     fingers of the same individual would not show such effects. 
B.   Similarly, inter-individual dermatoglyphic differences among
     fraX-females, to a very significant extent, would be due to X-
     inactivation mosaicisms as manifested in fingertips, etc.

III. MODIFIED STIX:  Statistical interpretation of dermatoglyphics data-
sets would be modified in that most fraX-individuals would not have skewed
X-inactivation and thus would have mosaic-like dermatoglyphic patterns --
i.e., some patterns would reflect activation of an X chromosome containing
a mutated FMR-1 and other patterns would reflect activation of the
person's X chromosome which is not mutated at FMR-1.

A. This intra-individual dermatoglypical mosaicism, if it is found to
exist (in mice? in humans?), would mean that "soft" statistical findings
in such studies would be anticipated and would be more significant than
their "softness" otherwise would suggest. 

B. If the aforementioned relationships are substantiated by findings among
mice and humans, then such results would suggest that in-brain mosaicisms
of X-inactivation might induce pleiotropy in data sets re: cognitive,
emotional, and behavioral traits as measured in females with X-chromosome
mutations affecting neural function, perhaps even for X-linked traits
other than fragile X. 

         ***       ***       Copyright 1995       ***       ***
                           Teresa C. Binstock

                    If, in a paper (etc) of your own,
            you use ideas original to this Internet document,
                    please cite:
                         Teresa C. Binstock 1995
                   <this news group or listserv group>
                          <file # within group>

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Comments in closing: as many of you have already noticed, I am thoroughly
a novice on the Internet. If I'm going out of protocol boundaries, please
let me know. Regardless, I appreciate comments re content of my postings
and calling to my attention of points to ponder, etc. 

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Teresa C. Binstock, Researcher                    article first posted
Developmental and Behavioral Neuroanatomy            onto Internet: 
B140 Child Development Unit                              6.28.95
The Children's Hospital
1056 E. 19th Avenue
Denver CO 80218 USA



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