Analysis of CAG and CCG repeats in Huntingtin gene among HD patients and normal populations of India

Abstract

We have analysed the distribution of CAG and adjacent polymorphic CCG repeats in the Huntingtin gene in 28 clinically diagnosed unrelated Huntington's disease (HD) patients and in normal individuals belonging to different ethnic groups of India. The range of expanded CAG repeats in HD patients varied from 41 to 56 repeats, whereas in normal individuals this number varied between 11 and 31 repeats. We identified six CCG alleles from a total of 380 normal chromosomes that were pooled across different ethnic populations of India. There were two predominant alleles: (CCG) 7 (72.6%) and (CCG) 10 (20%). We report here for the first time one four-repeat CCG allele which has not been found in any population so far. We found 30 haplotypes (two loci CAG-CCG) for 380 normal chromosomes. In the present study, no statistically significant preponderance of expanded HD alleles was found on either (CCG) 7 or (CCG) 10 backgrounds. Our studies suggest that the overall prevalence of HD in Indian populations may not be as high as in Western populations. Further studies are necessary to identify the origin of HD mutation in these populations.

Haplotype analysis of the CAG and CCG repeats in 21 Brazilian families with Huntington’s disease

“…27 In our sample, as in others, 22,23 the (CCG) 6 and (CCG) 8 alleles were rare. In Portuguese, Indian and Japanese populations, 23,27,28 multiple CCG alleles were associated with expanded CAG repeats within individual families. These findings suggest that one mutational event may have led to these differences in the number of CCG repeats.…”

“…The CCG polymorphic region may indicate the ancestral origin of the expanded CAG repeat allele that causes HD, 21 given that they are located in the same chromosomal region, only 12 bp apart. Each ethnic population shows a predominance of a certain number of CCG repeats that can vary from 6 to 12 repeats, 22 with the exception of a case reported by Pramanik et al, 23 in which four CCG repeats were identified.…”

Genetic background of Huntington disease in Croatia: Molecular analysis of CAG, CCG, and ?2642 (E2642del) polymorphisms

“…Analysis of the CAG repeat region among 44 HD patients (39-66 CAGs) and 51 normal individuals (9-34 CAGs) showed that the range of the repeat size was similar to previous reports in other populations (Andrew et al, 1993;Huntington's Disease Collaborative Research Group, 1993;Andrew and Hayden, 1995;Brandt et al, 1996;Pramanik et al, 2000). In addition, the mean CAG size of 102 normal chromosomes of Croatian origin (18.5 ± 3.5) was found to resemble that for a Western European populations (18.4 ± 3.7) and was considerably higher than the mean CAG lengths found on Black, Chinese, Japanese and Finnish normal chromosomes (16.5 ± 1.7) (Squitieri et al, 1994).…”

“…In this respect, populations of Western European descent, that have a higher prevalence rate of HD, have a higher frequency of the CCG allele 7, while in African Blacks, Japanese, Chinese and Finnish populations, where HD occurs more rarely, the CCG allele 10 is overpresented (Squitieri et al, 1994;Andrew and Hayden, 1995;Pramanik et al, 2000). In addition, the ∆2642 polymorphism which is not found at all in African and Asian populations is overpresented among HD cases of W. European descent Andrew and Hayden, 1995).…”

“…Variation of the prevalence of HD among different populations has been found to correlate with the frequency of certain polymorphic alleles on normal chromosomes, suggesting different origins for the HD mutation (Squitieri et al, 1994;Almqvist et al, 1995;Andrew and Hayden, 1995;Pramanik et al, 2000). In this respect, populations of Western European descent, that have a higher prevalence rate of HD, have a higher frequency of the CCG allele 7, while in African Blacks, Japanese, Chinese and Finnish populations, where HD occurs more rarely, the CCG allele 10 is overpresented (Squitieri et al, 1994;Andrew and Hayden, 1995;Pramanik et al, 2000).…”