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Title: Evidence for modifier genes that enhance the effect of the Pax-3 mutation, splotch-delayed (Sp{sup d}), on facial morphology: A model for studying the causes of variation of Waardenburg syndrome

Abstract

Waardenburg syndrome type I (WS1) is caused by autosomal dominant mutations of the gene coding for the PAX3 transcription factor. These mutations have variable penetrance and expressivity within and between families where they cause hypopigmentation, deafness and facially dysmorphic features. It has been suspected that changes of penetrance and expressivity in WS1 mutations are caused by familial variation in other loci which interact with or modify the expression of the PAX3 locus. Splotch mutations (Sp, Sp{sup d}, etc.) are the mouse homologs of WS1 mutations. Mutations in Pax-3 were first used to predict the map position and function of WS1 mutations. We now present morphometric evidence for alleles of modifier genes, originating from Mus spretus and segregating in an F{sub 1} backcross with Mus musculus, that modify the effects of Sp{sup d} on the structure of mouse facial bones. Variation caused by these mouse genes are precisely homologous to the familial variation we see in dystopia canthorum, the principal diagnostic feature of Waardenburg syndrome type I. The mouse modifier genes of Pax-3 identified by this analysis are now being mapped as a first step towards positional cloning human PAX3 modifier genes.

Authors:
; ;  [1]
  1. Michigan State Univ., East Lansing, MI (United States); and others
Publication Date:
OSTI Identifier:
133407
Report Number(s):
CONF-941009-
Journal ID: AJHGAG; ISSN 0002-9297; TRN: 95:005313-0135
Resource Type:
Journal Article
Journal Name:
American Journal of Human Genetics
Additional Journal Information:
Journal Volume: 55; Journal Issue: Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; PATIENTS; HEREDITARY DISEASES; PHENOTYPE; SENSE ORGANS DISEASES; DIAGNOSIS; GENES; GENE MUTATIONS; STRUCTURE-ACTIVITY RELATIONSHIPS; GENETIC MAPPING; FACE; MORPHOLOGY; MICE; DOMINANT MUTATIONS; DNA-CLONING

Citation Formats

Harrison, R W, Morell, R, and Friedman, T B. Evidence for modifier genes that enhance the effect of the Pax-3 mutation, splotch-delayed (Sp{sup d}), on facial morphology: A model for studying the causes of variation of Waardenburg syndrome. United States: N. p., 1994. Web.
Harrison, R W, Morell, R, & Friedman, T B. Evidence for modifier genes that enhance the effect of the Pax-3 mutation, splotch-delayed (Sp{sup d}), on facial morphology: A model for studying the causes of variation of Waardenburg syndrome. United States.
Harrison, R W, Morell, R, and Friedman, T B. 1994. "Evidence for modifier genes that enhance the effect of the Pax-3 mutation, splotch-delayed (Sp{sup d}), on facial morphology: A model for studying the causes of variation of Waardenburg syndrome". United States.
@article{osti_133407,
title = {Evidence for modifier genes that enhance the effect of the Pax-3 mutation, splotch-delayed (Sp{sup d}), on facial morphology: A model for studying the causes of variation of Waardenburg syndrome},
author = {Harrison, R W and Morell, R and Friedman, T B},
abstractNote = {Waardenburg syndrome type I (WS1) is caused by autosomal dominant mutations of the gene coding for the PAX3 transcription factor. These mutations have variable penetrance and expressivity within and between families where they cause hypopigmentation, deafness and facially dysmorphic features. It has been suspected that changes of penetrance and expressivity in WS1 mutations are caused by familial variation in other loci which interact with or modify the expression of the PAX3 locus. Splotch mutations (Sp, Sp{sup d}, etc.) are the mouse homologs of WS1 mutations. Mutations in Pax-3 were first used to predict the map position and function of WS1 mutations. We now present morphometric evidence for alleles of modifier genes, originating from Mus spretus and segregating in an F{sub 1} backcross with Mus musculus, that modify the effects of Sp{sup d} on the structure of mouse facial bones. Variation caused by these mouse genes are precisely homologous to the familial variation we see in dystopia canthorum, the principal diagnostic feature of Waardenburg syndrome type I. The mouse modifier genes of Pax-3 identified by this analysis are now being mapped as a first step towards positional cloning human PAX3 modifier genes.},
doi = {},
url = {https://www.osti.gov/biblio/133407}, journal = {American Journal of Human Genetics},
number = Suppl.3,
volume = 55,
place = {United States},
year = {Thu Sep 01 00:00:00 EDT 1994},
month = {Thu Sep 01 00:00:00 EDT 1994}
}