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PMID: 1969225 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Two progenitor cells for human oogonia inferred from pedigree data and the X-inactivation imprinting model of the fragile-X syndrome.

American journal of human genetics ·Vol. 46 ·No. 4 ·1990-04-00 ·Pages 696-719

Laird CD, Lamb MM, Thorne JL

Abstract

Laird has proposed that the human fragile-X syndrome is caused by abnormal chromosome imprinting. The analysis presented here supports and extends this proposal. Using published pedigrees that include DNA polymorphism (RFLP) data, we establish that the states of the fragile-X mutation termed "imprinted" and "nonimprinted" usually can be distinguished by the level of cytogenetic expression of the fragile-X chromosome. This information is then used to assess the state of the fragile-X allele in carrier progeny of individual women who inherited a nonimprinted fragile-X chromosome. From this assessment, an estimate is made of the frequency, in individual women, of primary oocytes with an imprinted fragile-X chromosome. The results of this analysis provide additional support for the specific model in which chromosome imprinting occurs in a female in, on average, half of her primary oocytes. This is the expected frequency if X-chromosome inactivation is the initial step in the imprinting of the mutant fragile-X allele. Moreover, this analysis suggests a biological explanation for peculiarities of fragile-X inheritance described by others as "clustering" and the "Sherman paradox." We interpret these peculiarities as consequences of a very small number of oogonial progenitor cells. Two progenitor cells for oogonia is the best integer estimate of the number of such cells at the time of the initial event that leads to chromosome imprinting.

MeSH Terms
Alleles Dosage Compensation, Genetic Female Fragile X Syndrome/genetics Humans Male Models, Genetic Mutation Oogonia Ovum Pedigree Polymorphism, Restriction Fragment Length Sex Chromosome Aberrations/genetics
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Laird C D
Department of Zoology, University of Washington, Seattle 98195.
Lamb M M
Thorne J L
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
Published
1990-04-00
Pages
696-719
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1683665
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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