Distribution and evolution of CTG repeats at the myotonin protein kinase gene in human populations.

Deka, Ranjan; Majumder, Partha P.; Shriver, Mark D.; Stivers, David; Zhong, Yixi; Yu, Ling; Barrantes, Ramiro; Yin, Shih‐Jiun; Miki, Tetsuro; Hundrieser, J.; Bunker, Clareann H.; McGarvey, Stephen T.; Sakallah, Sameer; Ferrell, Robert E.; Chakraborty, Ranajit

doi:10.1101/gr.6.2.142

Cited by 42 publications

(43 citation statements)

References 25 publications

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“…The most frequent allele was different between Caucasians and Asians: five repeats is the most common in European, and 12 repeats in Japanese [7,8]. In Koreans, a previous study reported the range of CTG repeats to be 5 to 34, and (CTG)11-14 as the predominant alleles [9].…”

Section: Discussionmentioning

confidence: 99%

Molecular and Clinical Characteristics of Myotonic Dystrophy Type 1 in Koreans

Kim

et al. 2008

Ann Lab Med

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Section: Discussionmentioning

confidence: 99%

Molecular and Clinical Characteristics of Myotonic Dystrophy Type 1 in Koreans

Kim

et al. 2008

Ann Lab Med

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“…These data include allele frequencies at 116 dinucleotide loci (details available on request), 3 neutral trinucleotide loci (D19S190, D19S261, and SCN1B), 1 disease trinucleotide locus (DM), and 12 tetranucleotide loci (D19S244-D19S47, D19S250-D19S255, and EPOR). Table 1 shows the summary results of the ANOVA of the natural logarithms of locus-and population-specific variances of allele sizes (lnV ijk ) for the first two sets of data (16)(17)(18)(19)(20). For both sets of data, the component of variation due to population differences is not significant (P Ͼ 0.75)-i.e., x j ϭ lnN j is nearly constant over all j in both sets of data.…”

Section: Datamentioning

confidence: 99%

“…The first set is described in refs. [16][17][18]. It includes allele frequencies at eight dinucleotide (FLT1, D13S118, D13S121, D13S71, D13S122, D13S197, D13S193, and D13S124), five trinucleotide (PLA2A, DM, SCA, DRPLA, and HD), and five tetranucleotide (THO1, CSF1R, F13A1, CYP19, and LPL) repeat loci in samples from nine populations (unrelated Caucasians from the Centre d'É tude du Polymorphisme Humain panel; Germans; Brazilian Whites; Brahmins from Uttar Pradesh, India; Sokoto from Nigeria; Benin; Brazilian Blacks; Japanese; and Chinese).…”

Section: Datamentioning

confidence: 99%

Relative mutation rates at di-, tri-, and tetranucleotide microsatellite loci

Chakraborty

Kimmel²,

Stivers³

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

375

247

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Using the generalized stepwise mutation model, we propose a method of estimating the relative mutation rates of microsatellite loci, grouped by the repeat motif. Applying ANOVA to the distributions of the allele sizes at microsatellite loci from a set of populations, grouped by repeat motif types, we estimated the effect of population size differences and mutation rate differences among loci. This provides an estimate of motif-type-specific mutation rates up to a multiplicative constant. Applications to four different sets of di-, tri-, and tetranucleotide loci from a number of human populations reveal that, on average, the non-disease-causing microsatellite loci have mutation rates inversely related to their motif sizes. The dinucleotides appear to have mutation rates 1.5-2 times higher than the tetranucleotides, and the non-disease-causing trinucleotides have mutation rates intermediate between the di-and tetranucleotides. In contrast, the disease-causing trinucleotides have mutation rates 3.9-6.9 times larger than the tetranucleotides. Comparison of these estimates with the direct observations of mutation rates at microsatellites indicates that the earlier suggestion of higher mutation rates of tetranucleotides in comparison with the dinucleotides may stem from a nonrandom sampling of tetranucleotide loci in direct mutation assays.The mutation rate () at genetic loci and the effective population size (N) are two basic parameters for understanding the genetic structure of a population. Numerous population genetic studies addressed the question of estimating these two quantities individually as well as simultaneously (1-3). For populations with large generation time and overlapping generations, direct estimation of effective population size is problematic (4). Likewise, mutation rates at most genetic loci are not large enough to be directly measured, and inference of true mutational events is also complicated by assumptions regarding biological relationships of the observed pedigrees (5, 6).One alternative is to estimate the mutation rates by indirect procedures that rely on allele frequency distributions in populations (1-3, 5, 7). In these studies it was assumed that (i) population is in a mutation-drift balance, so that the allele frequency distributions in populations could be expressed in terms of N, the product of effective population size (N), and the rate of mutation (); and (ii) that each mutation yields an allele previously not seen in the population (the infinite allele model). The first assumption is reasonable for most large populations, whereas the second may not apply to all loci. In particular, for microsatellite loci, where polymorphisms are caused by differences in the number of tandem repeats, the infinite allele model does not apply (8-10).Recent theoretical work suggests that the within-population variance of repeat unit sizes is proportional to the product of two basic parameters, N and (11, 12), and this relationship holds even when the pattern of mutational changes at microsatell...

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“…Analysis of the DMPK alleles of these individuals showed a tri-modal distribution of (CTG) n repeat size similar to that previously observed in other populations of predominantly European ancestry (Figure 1). 21,26,27 The sample was found to be in HardyWeinberg equilibrium (P ¼ 0.4). This suggests that although our study group was a selected group that had difficulty to conceive, it was not different from the general population with respect to the distribution of the DMPK alleles.…”

Section: Resultsmentioning

confidence: 99%

“…However, the distribution of the DMPK alleles within our study, which was not selected for ethnicity, but was largely French Canadian, showed a similar tri-modal pattern and prevalence of (CTG) 5 repeats as previously observed in other populations of predominantly European ancestry (Figure 1). 21,26,27 If infertility were associated with a change in transmission patterns, one would expect this to be reflected in the distribution of allele frequencies.…”

Section: Discussionmentioning

confidence: 99%

Transmission ratio distortion in the myotonic dystrophy locus in human preimplantation embryos

et al. 2006

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One form of myotonic dystrophy, dystrophia myotonica 1 (DM1), is caused by the expansion of a (CTG) n repeat within the dystrophia myotonica-protein kinase (DMPK) gene located in chromosome region 19q13.3. Unaffected individuals carry alleles with repeat size (CTG) 5 -37 , premutation carriers (CTG) 38 -49 and DM1 affected individuals (CTG) 50 -6000 . Preferential transmission both of expanded repeats from DM1-affected parents and larger DMPK alleles in the normal-size range have been reported in live-born offspring. To determine the moment in development when transmission ratio distortion (TRD) for larger normal-size DMPK alleles is generated, the transmission from heterozygous parents with one repeat within the (CTG) 5 -18 range (Group I repeat) and the other within the (CTG) 19 -37 range (Group II repeat) to human preimplantation embryos was analysed. A statistically significant TRD of 59% (95% confidence interval of 54 -64) in favour of Group II repeats from both mothers and fathers was observed in preimplantation embryos, which remained significant when female embryos were considered separately. In contrast, no significant TRD was detected for repeats from informative Group I/Group I parents. Our analysis showed that Group II repeats specifically were preferentially transmitted in human preimplantation embryos. We suggest that TRD, in Group II repeats at the DMPK locus, is likely to result from events occurring at or around the time of fertilisation.

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Distribution and evolution of CTG repeats at the myotonin protein kinase gene in human populations.

Cited by 42 publications

References 25 publications

Molecular and Clinical Characteristics of Myotonic Dystrophy Type 1 in Koreans

Molecular and Clinical Characteristics of Myotonic Dystrophy Type 1 in Koreans

Relative mutation rates at di-, tri-, and tetranucleotide microsatellite loci

Transmission ratio distortion in the myotonic dystrophy locus in human preimplantation embryos

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