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| MUTATIONAL BIAS PROVIDES A MODEL FOR THE EVOLUTION OF HUNTINGTONS-DISEASE AND PREDICTS A GENERAL INCREASE IN DISEASE PREVALENCE |
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| Author(s): RUBINSZTEIN DC, AMOS W, LEGGO J, GOODBURN S, RAMESAR RS, OLD J, BONTROP R, MCMAHON R, BARTON DE, FERGUSONSMITH MA |
| Source: NATURE GENETICS Volume: 7 Issue: 4 Pages: 525-530 Published: AUG 1994 |
| Times Cited: 95 References: 19 |
| Abstract: Huntington's disease (HD) correlates with abnormal expansion in a block of GAG repeats in the Huntington's disease gene. We have investigated HD evolution by typing GAG alleles in several human populations and in a variety of primates. We find that human alleles have expanded from a shorter ancestral state and exhibit unusual asymmetric length distributions. Computer simulations are used to show that the human state can be derived readily from a primate ancestor, without the need to invoke natural selection. The key element is a simple length-dependent mutational bias towards longer alleles. Our model can explain a number of empirical observations, and predicts an ever-increasing incidence of HD. |
| Document Type: Article |
| Language: English |
| Reprint Address: RUBINSZTEIN, DC (reprint author), ADDENBROOKES NHS TRUST, E ANGLIAN REG GENET SERV, GENET MOLEC LAB, BOX 158, CAMBRIDGE CB2 2QQ, CAMBS ENGLAND |
Addresses:
1. ADDENBROOKES NHS TRUST, DEPT CLIN GENET, CAMBRIDGE CB2 2QQ, CAMBS ENGLAND
2. UNIV CAMBRIDGE, DEPT GENET, CAMBRIDGE CB2 3EH, CAMBS ENGLAND
3. UNIV CAPE TOWN, DEPT HUMAN GENET, CAPE TOWN, SOUTH AFRICA
4. JOHN RADCLIFFE HOSP, INST MOLEC MED, OXFORD OX3 9DU, ENGLAND
5. TNO, MED BIOL LAB, 2280 RIJSWIJK, NETHERLANDS
6. UNIV CAMBRIDGE, DEPT PATHOL, CAMBRIDGE CB2 1QP, CAMBS ENGLAND |
| Publisher: NATURE PUBLISHING CO, 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 |
| Subject Category: Genetics & Heredity |
| IDS Number: PA832 |
| ISSN: 1061-4036 |
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