TY - JOUR
T1 - Patterns of instability of expanded CAG repeats at the ERDA1 locus in general populations
AU - Deka, Ranjan
AU - Guangyun, Sun
AU - Wiest, Jonathan
AU - Smelser, Diane
AU - Chunhua, Su
AU - Zhong, Yixi
AU - Chakraborty, Ranajit
N1 - Funding Information:
We thank Drs. C. H. Bunker, R. E. Ferrell, G. Flatz, and P. E. Smouse for providing various population DNA samples. This research is supported by U.S. Public Health Service Research grants GM 45861 and GM 41399.
PY - 1999
Y1 - 1999
N2 - A highly polymorphic CAG repeat locus, ERDA1, was recently described on human chromosome 17q21.3, with alleles as large as 50-90 repeats and without any disease association in the general population. We have studied allelic distribution at this locus in five human populations and have characterized the mutational patterns by direct observation of 731 meioses. The data show that large alleles (≥40 CAG repeats) are generally most common in Asian populations, less common in populations of European ancestry, and least common among Africans. We have observed a high intergenerational instability (46.3% ± 5.1%) of the large alleles. Although the mutation rate is not dependent on parental sex, paternal transmissions have predominantly resulted in contractions, whereas maternal transmissions have yielded expansions. Within this class of large alleles, the mutation rate increases concomitantly with increasing allele size, but the magnitude of repeat size change does not depend on the size of the progenitor allele. Sequencing of specific alleles reveals that the intermediate-sized alleles (30-40 repeats) have CAT/CAC interruptions within the CAG-repeat array. These results indicate that expansion and instability of trinucleotide repeats are not exclusively disease-associated phenomena. The implications of the existence of massively expanded alleles in the general populations are not yet understood.
AB - A highly polymorphic CAG repeat locus, ERDA1, was recently described on human chromosome 17q21.3, with alleles as large as 50-90 repeats and without any disease association in the general population. We have studied allelic distribution at this locus in five human populations and have characterized the mutational patterns by direct observation of 731 meioses. The data show that large alleles (≥40 CAG repeats) are generally most common in Asian populations, less common in populations of European ancestry, and least common among Africans. We have observed a high intergenerational instability (46.3% ± 5.1%) of the large alleles. Although the mutation rate is not dependent on parental sex, paternal transmissions have predominantly resulted in contractions, whereas maternal transmissions have yielded expansions. Within this class of large alleles, the mutation rate increases concomitantly with increasing allele size, but the magnitude of repeat size change does not depend on the size of the progenitor allele. Sequencing of specific alleles reveals that the intermediate-sized alleles (30-40 repeats) have CAT/CAC interruptions within the CAG-repeat array. These results indicate that expansion and instability of trinucleotide repeats are not exclusively disease-associated phenomena. The implications of the existence of massively expanded alleles in the general populations are not yet understood.
UR - http://www.scopus.com/inward/record.url?scp=0033362098&partnerID=8YFLogxK
U2 - 10.1086/302453
DO - 10.1086/302453
M3 - Article
C2 - 10364532
AN - SCOPUS:0033362098
SN - 0002-9297
VL - 65
SP - 192
EP - 198
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -