Human genetics. Measuring mutation in man.
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Antineoplastic Agents↗
Biomedical subjects
M F Lyon
Publications and source records attributed to M F Lyon.
X chromosomes and dosage compensation.
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Animals↗
Age related reactivation of an X-linked gene.
We have investigated age-related reactivation of the X chromosome by devising a model in which reactivation of a single gene in one cell among many can be identified. We have used mice with an X-autosomal translocation giving consistent non-random inactivation of the normal X (as judged by biochemical and cytogenetic techniques), that also carry a defective form of a histochemically demonstrable X-linked enzyme. When the gene for the normal enzyme was located on the inactivated normal X a uniformly negative histochemical picture would be predicted in doubly heterozygous animals. A very small proportion of enzyme-positive cells was found in young animals. This proportion increased very significantly with age, but the patch size did not change, showing that the result was not due to preferential division of enzyme-positive cells, but was instead due to the conversion of previously enzyme-negative to enzyme-positive cells. These observations provide the first evidence with a true X-linked gene for an age-related decrease in the stability of the X-inactivation mechanism.
Aging↗
The mapping of a cDNA from the human X-linked Duchenne muscular dystrophy gene to the mouse X chromosome.
The recent discovery of sequences at the site of the Duchenne muscular dystrophy (DMD) gene in humans has opened up the possibility of a detailed molecular analysis of the genes in humans and in related mammalian species. Until relatively recently, there was no obvious mouse model of this genetic disease for the development of therapeutic strategies. The identification of a mouse X-linked mutant showing muscular dystrophy, mdx, has provided a candidate mouse genetic homologue to the DMD locus; the relatively mild pathological features of mdx suggest it may have more in common with mutations of the Becker muscular dystrophy type at the same human locus, however. But the close genetic linkage of mdx to G6PD and Hprt on the mouse X chromosome, coupled with its comparatively mild pathology, have suggested that the mdx mutation may instead correspond to Emery Dreifuss muscular dystrophy which itself is closely linked to DNA markers at Xq28-qter in the region of G6PD on the human X chromosome. Using an interspecific mouse domesticus/spretus cross, segregating for a variety of markers on the mouse X chromosome, we have positioned on the mouse X chromosome sequences homologous to a DMD cDNA clone. These sequences map provocatively close to the mdx mutation and unexpectedly distant from sparse fur, spf, the mouse homologue of OTC (ornithine transcarbamylase) which is closely linked to DMD on the human X chromosome.
Alleles↗
Mouse globin gene nomenclature.
A new system of nomenclature for haplotypes, genes, alleles, and mutant alleles in the mouse alpha- and beta-globin gene complexes was formulated at a meeting of workers in the field and is presented here.
Alleles↗
The history of X-chromosome inactivation and relation of recent findings to understanding of human X-linked conditions.
This paper represents the text of two lectures given on the occasion of a Workshop on the X-Chromosome held at Hacettepe University, Ankara, in September 1994. The history of the development of ideas concerning the mechanism of X-chromosome inactivation is traced from the finding of the sex chromatin body in 1949. Important recent findings concern the Xist gene, which is a candidate gene for the X-inactivation center, from which inactivation is initiated. These recent findings shed new light on the abnormalities seen in human patients with X-linked genetic diseases or with aneuploidy of the X-chromosome.
Dosage Compensation, Genetic↗