Segregation distortion of the CTG repeats at the myotonic dystrophy locus

Journal Article · Mon Jul 01 04:00:00 EDT 1996 · American Journal of Human Genetics

OSTI ID:443742

Chakraborty, R; Stivers, D N ^[1]; Deka, R; Yu, Ling M; Shriver, M D; Ferrell, R E ^[2]

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1. Univ. of Texas Houston Health Science Center, Houston, TX (United States)
2. Univ. of Pittsburgh Graduate School of Public Health, Pittsburgh, PA (United States)

Myotonic dystrophy (DM), an autosomal dominant neuromuscular disease, is caused by a CTG-repeat expansion, with affected individuals having {ge}50 repeats of this trinucleotide, at the DMPK locus of human chromosome 19q13.3. Severely affected individuals die early in life; the milder form of this disease reduces reproductive ability. Alleles in the normal range of CTG repeats are not as unstable as the (CTG){sub {ge}50} alleles. In the DM families, anticipation and parental bias of allelic expansions have been noted. However, data on mechanism of maintenance of DM in populations are conflicting. We present a maximum-likelihood model for examining segregation distortion of CTG-repeat alleles in normal families. Analyzing 726 meiotic events in 95 nuclear families from the CEPH panel pedigrees, we find evidence of preferential transmission of larger alleles (of size {le}29 repeats) from females (the probability of transmission of larger alleles is .565 {plus_minus} 0.03, different from .5 at P {approx} .028). There is no evidence of segregation distortion during male meiosis. We propose a hypothesis that preferential transmission of larger CTG-repeat alleles during female meiosis can compensate for mutational contraction of repeats within the normal allelic size range, and reduced viability and fertility of affected individuals. Thus, the pool of premutant alleles at the DM locus can be maintained in populations, which can subsequently mutate to the full mutation status to give rise to DM. 31 refs., 1 fig., 5 tabs.

• OSTI ID: 443742
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 1 Vol. 59; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
DOMINANT MUTATIONS
GENE MUTATIONS
GENES
GENETIC MAPPING
GENETICS
GENOTYPE
HEREDITARY DISEASES
HUMAN CHROMOSOME 19
MEIOSIS
MORTALITY
MUSCLES
MUTATION FREQUENCY
MUTATIONS
NERVOUS SYSTEM DISEASES
NUCLEOTIDES
PATIENTS
POLYMERASE CHAIN REACTION
REPRODUCTIVE DISORDERS
SIZE
STATISTICAL MODELS