PCR analysis of four length-polymorphic loci in Korean population for genotyping

On human chromosomes, a short sequence of DNA is known to repeat a number of times. These repeats are called variable number of tandem repeat (VNTR) or short tandem repeat (STR) which has a short repeat core. VNTR and STR are used in the field of forensic science, evolution, and anthropology. In this work, we examined allele frequencies of one VNTR (YNZ22) and three STRs (NeuR, D21S11, Humth01) in a Korean population sample by polymerase chain reaction (PCR) followed by high-resolution polyacrylamide gel electrophoresis (PAGE) with silver stain. Subsequently, the polymorphism information content (PIC) was calculated: the highest PIC was observed in the NeuR locus (0.95680) and lowest in the Humth01 locus (0.75809).     

FMR1 CGG repeat distribution and linked microsatellite-SNP haplotypes in normal Mexican Mestizo and indigenous populations

The (CGG)n repeat size distribution in the FMR1 gene was studied in healthy individuals: 80 X chromosomes of Mexican Mestizos from Mexico City and 33 X chromosomes of Mexican Amerindians from three indigenous communities (Purepechas, Nahuas, and Tzeltales), along with alleles and haplotypes defined by two microsatellite polymorphic markers (DXS548 and FRAXAC1) and two single nucleotide polymorphisms (FMRA and FMRB). Genetic frequencies of Mestizo and Amerindian subpopulations were statistically similar in almost all cases and thus were considered one population for comparisons with other populations. Sixteen (CGG)n alleles in the 17-38 size range were observed, and the most common were the 25 (38.0%), 26 (28.3%), and 24 (12.3%) repeat alleles. This pattern differs from most other populations reported, but a closer relation to Amerindian, European, and African populations was found, as expected from the historical admixture that gave rise to Mexican Mestizos. The results of the CA repeats analysis at DXS548-FRAXAC1 were restricted to nine haplotypes, of which haplotypes 7-4 (52.2%), 8-4 (23.8%), and 7-3 (11.5%) were predominant. The modal haplotype 7-4, instead of the nearly universal haplotype 7-3, had been reported exclusively in Eastern Asian populations. Likewise, only seven different FRAXAC1-FMRA-FMRB haplotypes were observed, including five novel haplotypes (3TA, 4TA, 3 - A, 4 - A, and 5 - A), compared with Caucasians. Of these, haplotypes - A (78.7%) and 3 - A (13.2%) were the most common in the Mexican population. These data suggest a singular but relatively low genetic diversity at FMR1 in the studied Mexican populations that may be related to the recent origin of Mestizos and the low admixture rate of Amerindians.     

用DNA多态性分析福建,江西和浙江3省畲族的亲缘关系

为分析福建,江西和浙江３省畲族之间的关系,用聚合酶链反应（ＰＣＲ）对上述３省的３代均为畲族的无关个体的载脂蛋白Ｂ基因和Ｄ１７Ｓ３０位点的数目可变的串联重复（ＶＮＴＲ）序列进行研究。结果为：６个共有的ａｐｏＢ ＶＮＴＲ和５个共有的Ｄ１７Ｓ３０ ＶＮＴＲ等位基因在３省畲族中的分布相同,为进一步在基因水下上研究它们的亲缘关系奠定了基础。本文报道的检测ＤＮＡ多态性的方法在研究民族起源,变迁和民族识别以及各     

Polymorphic DNA haplotypes at the phenylalanine hydroxylase (PAH) locus in European families with phenylketonuria (PKU)

DNA haplotype data from the phenylalanine hydroxylase (PAH) locus are available from a number of European populations as a result of RFLP testing for genetic counseling in families with phenylketonuria (PKU). We have analyzed data from Hungary and Czechoslovakia together with published data from five additional countries--Denmark, Switzerland, Scotland, Germany, and France--representing a broad geographic and ethnographic range. The data include 686 complete chromosomal haplotypes for eight RFLP sites assayed in 202 unrelated Caucasian families with PKU. Forty-six distinct RFLP haplotypes have been observed to date, 10 unique to PKU-bearing chromosomes, 12 unique to non-PKU chromosomes, and the remainder found in association with both types. Despite the large number of haplotypes observed (still much less than the theoretical maximum of 384), five haplotypes alone account for more than 76% of normal European chromosomes and four haplotypes alone account for more than 80% of PKU-bearing chromosomes. We evaluated the distribution of haplotypes and alleles within these populations and calculated pairwise disequilibrium values between RFLP sites and between these sites and a hypothetical PKU "locus." These are statistically significant differences between European populations in the frequencies of non-PKU chromosomal haplotypes (P = .025) and PKU chromosomal haplotypes (P much less than .001). Haplotype frequencies of the PKU and non-PKU chromosomes also differ significantly (P much less than .001. Disequilibrium values are consistent with the PAH physical map and support the molecular evidence for multiple, independent PKU mutations in Caucasians. However, the data do not support a single geographic origin for these mutations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Molecular-genetic analysis of VNTR polymorphism in alleles of the phenylalanine hydroxylase gene in inhabitants of the Volga-Urals region

Molecular genetic analysis of the VNTR alleles at the phenylalanine hydroxylase (PAH) gene was carried out in seven Volga-Ural ethnic groups (Bashkirs, Tatars, Chuvashes, Maris, Mordovians, Udmurts, and Komis). The PCR fragments revealed included alleles of 380, 440, 470, 500, 530, 560, and 650 bp, containing 3, 5, 6, 7, 8, 9, and 12 repeat copies, respectively. Substantial heterogeneity of the populations in respect to the distribution and frequency of the VNTR alleles and genotypes was demonstrated. The indices of observed and theoretical heterozygosity of the PAH VNTR alleles were calculated. The mean heterozygosity index was 70.02%. This high index value along with the established differentiation of the populations in respect to the frequency distribution of the VNTR alleles and PAH genotypes permitted the conclusion that the given polymorphic locus can serve as a highly informative marker for examination of the genetic structure of the Volga-Ural populations.     

VNTR alleles associated with the alpha-globin locus are haplotype and population related.

The human alpha-globin complex contains several polymorphic restriction-enzyme sites (i.e., RFLPs) linked to form haplotypes and is flanked by two hypervariable VNTR loci, the 5' hypervariable region (HVR) and the more highly polymorphic 3'HVR. Using a combination of RFLP analysis and PCR, we have characterized the 5'HVR and 3'HVR alleles associated with the alpha-globin haplotypes of 133 chromosomes, and we here show that specific alpha-globin haplotypes are each associated with discrete subsets of the alleles observed at these two VNTR loci. This statistically highly significant association is observed over a region spanning approximately 100 kb. With the exception of closely related haplotypes, different haplotypes do not share identically sized 3'HVR alleles. Earlier studies have shown that alpha-globin haplotype distributions differ between populations; our current findings also reveal extensive population substructure in the repertoire of alpha-globin VNTRs. If similar features are characteristic of other VNTR loci, this will have important implications for forensic and anthropological studies.     

VNTR loci reveal differentiation between and structure within populations of the eastern barred bandicoot Perameles gunnii

The Eastern Barred Bandicoot Perameles gunnii has declined in abundance within mainland south-eastern Australia, to a relict wild population of less than 100 individuals in Hamilton, Victoria. It is more common, but is also declining in Tasmania. Genomic DN A variability was compared within and between surviving populations of P. gunnii using variable number of tandem repeat (VNTR) markers in one of two ways. First, average percentage differences (APDs) were determined between profiles for two VNTR probe—endonuclease combinations. Secondly, because one of these combinations revealed two multiallelic VNTR loci, genotypes were assigned and analysed for homogeneity of allele frequencies among subpopulations, for deviation of heterozygosity from Hardy-Weinberg equilibrium within populations and for genetic structuring among individuals from different subpopulations. The results of both the APD and defined locus approaches showed consistent trends within and between populations. Genetic variability was higher among mainland P. gunnii than in Tasmanian populations (higher APDs, number of alleles, and heterozygosity at one locus), despite the known decline and subdivision of the Hamilton population. Eleven per cent of the variability detected in Hamilton was attributed to genetic differentiation between east and west subdivisions of the population. Departure from random mating indicating local inbreeding within collecting localities was evident for one locus in both north and south Tasmania, particularly at one locality. AH alleles at both loci were unique to either Hamilton or Tasmanian P. gunnii. The initial captive colony contains high heterozygosity for these loci. It is concluded that VNTR markers can be of benefit for use in studies of population differentiation and for conservation management.     

No evidence for strong recent positive selection favoring the 7 repeat allele of VNTR in the DRD4 gene

The human dopamine receptor D4 (DRD4) gene contains a 48-bp variable number of tandem repeat (VNTR) in exon 3, encoding the third intracellular loop of this dopamine receptor. The DRD4 7R allele, which seems to have a single origin, is commonly observed in various human populations and the nucleotide diversity of the DRD4 7R haplotype at the DRD4 locus is reduced compared to the most common DRD4 4R haplotype. Based on these observations, previous studies have hypothesized that positive selection has acted on the DRD4 7R allele. However, the degrees of linkage disequilibrium (LD) of the DRD4 7R allele with single nucleotide polymorphisms (SNPs) outside the DRD4 locus have not been evaluated. In this study, to re-examine the possibility of recent positive selection favoring the DRD4 7R allele, we genotyped HapMap subjects for DRD4 VNTR, and conducted several neutrality tests including long range haplotype test and iHS test based on the extended haplotype homozygosity. Our results indicated that LD of the DRD4 7R allele was not extended compared to SNP alleles with the similar frequency. Thus, we conclude that the DRD4 7R allele has not been subjected to strong recent positive selection.     

CTG repeats distribution and Alu insertion polymorphism at myotonic dystrophy (DM) gene in Amhara and Oromo populations of Ethiopia

Myotonic dystrophy (DM) is a dominantly inherited neuromuscular disease, highly variable and multisystemic, which is caused by the expansion of a CTG repeat located in the 3′ untranslated region of the DMPK gene. Normal alleles show a copy number of 5–37 repeats on normal chromosomes, amplified to 50–3000 copies on DM chromosomes. The trinucleotide repeat shows a trimodal allele distribution in the majority of the examined population. The first class includes alleles carrying (CTG)₅, the second class, alleles in the range 7–18 repeats, and the third class, alleles (CTG)_{≥ 19}. The frequency of this third class is directly related to the prevalence of DM in different populations, suggesting that normal large-sized alleles predispose toward DM. We studied CTG repeat allele distribution and Alu insertion and/or deletion polymorphism at the myotonic dystrophy locus in two major Ethiopian populations, the Amhara and Oromo. CTG allele distribution and haplotype analysis on a total of 224 normal chromosomes showed significant differences between the two ethnic groups. These differences have a bearing on the out-of-Africa hypothesis for the origin of the DM mutation. In addition, (CTG)_{≥ 19} alleles were exclusively detected in the Amhara population, confirming the predisposing role of these alleles compared with the DM expansion-mutation. Electronic Publication     

A minisatellite and a microsatellite polymorphism within 1.5 kb at the human muscle glycogen phosphorylase (PYGM) locus can be amplified by PCR and have combined informativeness of PIC 0.95.

We sequenced a genomic clone (pMCMP1), previously reported to detect a VNTR polymorphism at the PYGM locus, and found a dinucleotide repeat segment (CA)14(GA)25 and a complex (AT)-repeat-rich segment containing 63 repeats spanning 160 bp. Resolution of PCR-amplified genomic DNA from the (CA)(GA) repeat region on DNA sequencing gels revealed a highly informative polymorphism with alleles differing by 2-bp intervals and ranging in size from 156 to 190 bp. Among three racial groups, a total of 18 alleles were observed. Fourteen alleles were observed in Caucasians (PIC 0.89), 12 alleles in American Blacks (PIC 0.89), and 9 alleles in Pima Indians (PIC 0.73). PCR amplification of the (AT) repeat region and resolution of the products on DNA sequencing gels revealed a complex variable length polymorphism with alleles distributed in size from 367 to 970 bp. Twenty-eight alleles were found in American Blacks (PIC 0.94), 6 alleles in Pima Indians (PIC 0.70), and 11 alleles in Caucasians (PIC 0.71). Comparison of the previously described VNTR RFLP alleles visualized by Southern hybridization to the PCR products described in this report demonstrated that the polymorphism described in both assays was identical. However, a larger number of alleles could be detected from the PCR-amplified products. Combined informativeness, PIC 0.95, for the two polymorphisms was determined from haplotype analysis of 100 Caucasian chromosomes. Therefore, for genotyping purposes, informativeness is maximized from using both polymorphisms.     

A population genetic study of six VNTR loci in three ethnically defined populations.

To investigate the population genetic characteristics of VNTR polymorphisms in human populations, we have studied the allele frequency distribution of six VNTR loci (D1S57, RB1, D1S77, D1S61, alpha-globin 5'HVR, D1S76) in three well-defined populations (Kachari of Northeast India; Dogrib Indian of Canada; and New Guinea Highlander of Papua New Guinea). Even though the number of alleles sampled is limited, 48 to 92 alleles per locus per population, significant variation is noticed in the number of alleles per locus for all the populations. Using alternate summary measures, we have observed that genotype distributions at the six VNTR loci apparently conform to their respective Hardy-Weinberg predictions. Multilocus genotype profiles of the individuals in each of the three populations suggest that the VNTR alleles are independently segregating with the exception of the two linked loci D1S76 and D1S77. Lack of fit of all VNTR loci to one particular model of mutational change, either the Infinite Allele Model or the Stepwise Mutation Model, suggests more than one mechanism for production of new VNTR alleles. This study also indicates that increased heterozygosity at VNTR loci in comparison to protein and blood group loci may lead to more accurate estimates of genetic distance.     

Modelling survival and allele complementation in the evolution of genomes with polymorphic loci

We have simulated the evolution of sexually reproducing populations composed of individuals represented by diploid genomes. A series of eight bits formed an allele occupying one of 128 loci of one haploid genome (chromosome). The environment required a specific activity of each locus, this being the sum of the activities of both alleles located at the corresponding loci on two chromosomes. This activity is represented by the number of bits set to zero. In a constant environment the best fitted individuals were homozygous with alleles’ activities corresponding to half of the environment requirement for a locus (in diploid genome two alleles at corresponding loci produced a proper activity). Changing the environment under a relatively low recombination rate promotes generation of more polymorphic alleles. In the heterozygous loci, alleles of different activities complement each other fulfilling the environment requirements. Nevertheless, the genetic pool of populations evolves in the direction of a very restricted number of complementing haplotypes and a fast changing environment kills the population. If simulations start with all loci heterozygous, they stay heterozygous for a long time.     

VNTR polymorphism of the DRD4 locus in different Pakistani ethnic groups

The present study was designed to investigate the dopamine receptor D4 (DRD4) locus variable number of tandem repeat (VNTR) allelic distribution in different Pakistani ethnic groups. DNA samples from nine different ethnic groups of Pakistan were analyzed. Greek and Somali samples were included as representatives of the European and African populations, respectively. Pakistani, Greek, and Somali populations were also compared to the published data on different world populations. The allelic distribution revealed that the four-repeat allele was the most common allele in all the Pakistani ethnic groups as is in different other world populations, followed by the seven- and two-repeat alleles. To study the evolutionary relationship of the Pakistani ethnic groups among themselves and with a few other world populations, multidimensional scaling based on the allelic frequencies of the DRD4 VNTR was obtained. This analysis grouped most of the Pakistani ethnic groups together and closer to the European and Middle Eastern populations, except for the Mohanna from Sindh, who grouped with the African populations. In addition, the Somali and the Greek samples analyzed in this study grouped closer to the previous data obtained on the African and European populations, respectively.     

Polymorphisms distinguishing different mouse species and t haplotypes.

Three anonymous chromosome 17 DNA markers, D17Tu36, D17Tu43, and D17Le66B, differentiate between house mouse species and/or between t chromosomes. The D17Tu36 probe, which maps near the Fu locus and to the In(17)4 on t chromosomes, identifies at least 15 haplotypes, each haplotype characterized by a particular combination of DNA fragments obtained after digestion with the Taq I restriction endonuclease. Ten of these haplotypes occur in Mus domesticus, while the remaining five occur in M. musculus. In each of these two species, one haplotype is borne by t chromosomes while the other haplotypes are present on non-t chromosomes. The D17Tu43 probe, which maps near the D17Leh122 locus and to the In(17)3 on t chromosomes, also identifies at least 15 haplotypes in Taq I DNA digests, of which nine occur in M. domesticus and six in M. musculus. One of the nine M. domesticus haplotypes is borne by t chromosomes, the other haplotypes are borne by non-t chromosomes; two of the six M. musculus haplotypes are borne by t chromosomes and the remaining four by non-t chromosomes. Some of the D17Tu43 haplotypes are widely distributed in a given species, while others appear to be population-specific. Exceptions to species-specificity are found only in a few mice captured near the M. domesticus-M. musculus hybrid zone or in t chromosomes that appear to be of hybrid origin. The D17Leh66B probe, which maps to the In(17)2, distinguishes three haplotypes of M. domesticus-derived t chromosomes and one haplotype of M. musculus-derived t chromosomes. Because of these characteristics, the three markers are well suited for the study of mouse population genetics in general and of t chromosome population genetics in particular. A preliminary survey of wild M. domesticus and M. musculus populations has not uncovered any evidence of widespread introgression of genes from one species to the other; possible minor introgressions were found only in the vicinity of the hybrid zone. Typing of inbred strains has revealed the contribution of only M. domesticus DNA to the chromosome 17 of the laboratory mouse.     

Haplotype study of intermediate-length alleles at the fragile X (FMR1) gene: ATL1, FMRb, and microsatellite haplotypes differ from those found in common-size FMR1 alleles

The CGG repeat within the X-chromosome-linked FMR1 gene, which in hyperexpansion (> 200 copies) results in fragile X syndrome, is highly polymorphic. The mechanism of expansion is not well understood, but CGG repeats called intermediate-length or gray zone alleles (approximately equal 35-60 repeats) are thought to make up the FMR1 alleles showing initial steps in this expansion process. It has been hypothesized that the background haplotype of these alleles plays a role in their susceptibility to expansion. In this study we investigate whether or not the frequencies of alleles and haplotypes at four marker loci in the FMR1 gene region (microsatellites DXS548 and FRAXAC1 and SNPs ATL1 and FMRb) in 84 intermediate-length male chromosomes differ from those in 94 common-size male alleles. The ATL1*G and FMRB*A alleles were more frequent among intermediate-length alleles than among common alleles. In addition, the DXS548-FRAXAC1 T50-T42 and T40-T42 haplotypes were strongly associated with intermediate-length alleles between 41 and 60 CGG repeats (p < 0.001). Two extended haplotypes, DXS548-FRAXAC1-ATL1-FMRb T50-T42-G-A and T40-T42-G-A, are strongly associated (p < 0.001) with intermediate-length alleles between 41 and 60 CGG repeats, and these haplotypes have also been reported as fragile X associated haplotypes in European populations. These data suggest that these haplotypes are among the most susceptible to further expansion among the intermediate-length alleles. T50-T42-G-A was also much more prevalent in males with 35-40 CGG repeats than in males with common-size alleles. ATL1 did not increase discrimination among intermediate-length alleles beyond that detected by DXS548-FRAXAC1 haplotypes, but the FMRb locus did, particularly for the DXS548-FRAXAC1-ATL1 T50-T42-G and T40-T42-G haplotypes. Comparison with fragile X associated haplotypes, from the literature, suggests that repeat hyperexpansion occurs most frequently on chromosomes carrying FMRB*A. Within the intermediate-length allele category, however, there were some significant differences in haplotype frequencies between smaller and larger alleles, and this finding has implications for future studies.     

Minisatellite and microsatellite length variation at a complex bovine VNTR locus

Length variation at the BTGL1 variable number of tandem repeat (VNTR ) locus, which includes both minisatellite and microsatellite motifs, was examined in a wide sample of cattle. A total of 22 alleles were uncovered. The distribution of allele size variation implicated mechanisms involving both minisatellite and microsatellite sequences. This was confirmed by direct sequencing of two alleles. Differences between the two alleles involved repeat number variation of microsatellite motifs and a complex event involving the minisatellite motif, but point mutations were not observed.     

Variable tandem repeat VcA of Vibrio cholerae

Computer analysis revealed seven potential variable-number tandem-repeat (VNTR) loci in the Vibrio cholerae genome. Specific primers were designed to amplify locus VcA located on chromosome 2 and containing a TGCTGT repeat. The locus was found in all tested strains from a V. cholerae strain collection, the repeat number varying 3 to 23. In total, 14 VcA alleles were observed. The VcA locus was proposed as a marker for the molecular typing of V. cholerae strains.     

Linkage disequilibrium between alleles at highly polymorphic mini- and micro-satellite loci of Theileria parva isolated from cattle in three regions of Kenya

Theileria parva schizont-infected lymphocyte culture isolates from western, central and coastal Kenya were analysed for size polymorphism at 30 T. parva-specific variable number tandem repeat (VNTR) loci using a panel of mini- and micro-satellite markers. The mean number of alleles ranged from 3 to 11 at individual loci and 183 distinct alleles were observed in total, indicating high genetic diversity within the T. parva gene pool in Kenyan cattle. The frequency distribution of the length variation of specific alleles among isolates ranged from normal to markedly discontinuous. Genetic relationships between isolates were analysed using standard indices of genetic distance. Genetic distances and dendrograms derived from these using neighbour-joining algorithms did not indicate significant clustering on a geographical basis. Analysis of molecular variance demonstrated that the genetic variation between individual isolates was 72%, but only 2.3% when isolates from different regions were pooled. Both these observations suggest minimal genetic sub-structuring relative to geographical origin. Linkage disequilibrium was observed between pairs of loci within populations, as in certain Ugandan T. parva populations. A novel observation was that disequilibrium was also detected between alleles at three individual pairs of VNTR loci when isolates from the three regional meta-populations were pooled for analysis.     

Associations between mutations and a VNTR in the human phenylalanine hydroxylase gene.

The HindIII RFLP in the human phenylalanine hydroxylase (PAH) gene is caused by the presence of an AT-rich (70%) minisatellite region. This region contains various multiple of 30-bp tandem repeats and is located 3 kb downstream of the final exon of the gene. PCR-mediated amplification of this region from haplotyped PAH chromosomes indicates that the previously reported 4.0-kb HindIII allele contains three of these repeats, while the 4.4-kb HindIII allele contains 12 of these repeats. The 4.2-kb HindIII fragment can contain six, seven, eight, or nine copies of this repeat. These variations permit more detailed analysis of mutant haplotypes 1, 5, 6, and, possibly, others. Kindred analysis in phenylketonuria families demonstrates Mendelian segregation of these VNTR alleles, as well as associations between these alleles and certain PAH mutations. The R261Q mutation, associated with haplotype 1, is associated almost exclusively with an allele containing eight repeats; the R408W mutation, when occurring on a haplotype 1 background, may also be associated with the eight-repeat VNTR allele. Other PAH mutations associated with haplotype 1, R252W and P281L, do not appear to segregate with specific VNTR alleles. The IVS-10 mutation, when associated with haplotype 6, is associated exclusively with an allele containing seven repeats. The combined use of this VNTR system and the existing RFLP haplotype system will increase the performance of prenatal diagnostic tests based on haplotype analysis. In addition, this VNTR may prove useful in studies concerning the origins and distributions of PAH mutations in different human populations.     

Insights into the mutational history and prevalence of SCA1 in the Indian population through anchored polymorphisms

There is a wide variation in prevalence of spinocerebellar ataxia type 1 (SCA1) in different populations. In the present study, we observed SCA1 in ∼22% (37/167 families) of the autosomal dominant cerebellar ataxias (ADCAs) in the Indian population. We investigated the role of various genetic factors like repeat length, interruption pattern and chromosomal background in predisposing the repeats to instability in these families. We analyzed 12 markers (9 SNPs and 3 microsatellite markers) and found 3 of them, spanning a region of ∼65 kbp to be linked with the disease locus in the Indian population. The haplotype C-4-C defined by rs1476464 (SNP9)-D6S288-rs2075974 (SNP1), which was extremely rare in nonaffected chromosomes (∼3%), was observed to be significantly (P<0.0000) associated with the expanded chromosomes in ∼44% of SCA1 families. This haplotype was found in all nonhuman primates. SNP1 (C/T), which showed a skewed allelic distribution between large (LN > 30 repeats) and small normal (SN ≤ 30 repeats) alleles (P<0.0000) had similar allelic distribution (P=0.3477) in LN and expanded alleles. Our study suggested that LN and expanded chromosomes linked with the ancestral C allele of SNP1 might have originated simultaneously during evolution by the lengthening of repeats. The LN alleles might have accumulated repeat stabilizing non-CAG interruptions during this process. Similar proportions of T allele in SN with single interruptions, LN and expanded chromosomes lend credence to the origin of expanded alleles from singly-interrupted chromosomes. Our analyses using markers linked (anchoring) to SCA1 suggest that prevalence of SCA1 is correlated to both repeat length and number of interruptions in the Indian population. The spectrum of these alleles also points toward the antiquity of SCA1 mutation in the Indian population.Electronic Supplementary Material Supplementary material is available for this article at