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1.
The effect of CAT trinucleotide interruptions on the age at onset of spinocerebellar ataxia type 1 (SCA1)
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Z. Matsuyama Y. Izumi M. Kameyama H. Kawakami S. Nakamura 《Journal of medical genetics》1999,36(7):546-548
The effect of CAT trinucleotide interruptions in the CAG trinucleotide repeats of the SCA1 gene on the age at onset of spinocerebellar ataxia type 1 (SCA1) was investigated. The number of CAG repeats in SCA1 was determined by polymerase chain reaction (PCR) analysis, and the presence of CAT interruptions was assessed on the basis of the sensitivity of the PCR products to the restriction endonuclease SfaNI, which recognises CAT trinucleotides. Only one in 17 expanded SCA1 alleles from 17 SCA1 patients was interrupted by CAT. The SfaNI sensitive SCA1 allele from this single patient contained 58 CAG repeats, which would predict an age at onset of SCA1 of 22.0 years, in contrast to the actual 50 years. In addition, the brain stem atrophy of this patient was mild compared with that of a patient with 52 uninterrupted CAG repeats. A sequence analysis showed that the repeat portion of the patient contained (CAG)45CATCAG CAT(CAG)10. From these results, we suggest that the age at onset of SCA1 is not determined by the total number of CAG repeats (58) but by the number of uninterrupted CAG repeats. 相似文献
2.
CAG repeat instability at SCA2 locus: anchoring CAA interruptions and linked single nucleotide polymorphisms. 总被引:4,自引:0,他引:4
S Choudhry M Mukerji A K Srivastava S Jain S K Brahmachari 《Human molecular genetics》2001,10(21):2437-2446
Spinocerebellar ataxia 2 (SCA2) is an autosomal dominant neurodegenerative disorder that results from the expansion of a cryptic CAG repeat within the exon 1 of the SCA2 gene. The CAG repeat in normal individuals varies in length from 14 to 31 repeats and is frequently interrupted by one or more CAA triplets, whereas the expanded alleles contain a pure uninterrupted stretch of 34 to 59 CAG repeats. We have previously reported the presence of a limited pool of 'ancestral' or 'at risk' haplotypes for the expanded SCA2 alleles in the Indian population. We now report the identification of two novel single nucleotide polymorphisms (SNPs) in exon 1 of the SCA2 gene and their characterization in 215 normal and 64 expanded chromosomes. The two biallelic SNPs distinguished two haplotypes, GT and CC, each of which formed a predominant haplotype associated with normal and expanded SCA2 alleles. All the expanded alleles segregated with CC haplotype, which otherwise was associated with only 29.3% of the normal chromosomes. CAA interspersion analysis revealed that majority of the normal alleles with CC haplotype were either pure or lacked the most proximal 5' CAA interruption. The repeat length variation at SCA2 locus also appeared to be polar with changes occurring mostly at the 5' end of the repeat. Our results demonstrate that CAA interruptions play an important role in conferring stability to SCA2 repeat and their absence predisposes alleles towards instability and pathological expansion. Our study also provides new haplotypes associated with SCA2 that should prove useful in further understanding the mutational history and mechanism of repeat instability at the SCA2 locus. 相似文献
3.
Pornprot Limprasert Nassim Nouri Chamnong Nopparatana Prescott L. Deininger Bronya J.B. Keats 《American journal of medical genetics. Part A》1997,74(5):488-493
The CAG repeat tract at the autosomal dominant spinocerebellar ataxia type 1 (SCA1) locus was analyzed in SCA1 families and French-Acadian, African-American, Caucasian, Greenland Inuit, and Thai populations. The normal alleles had 9–37 repeats, whereas disease alleles contained 44–64 repeats. The CAG repeat tract contained one or two CAT interruptions in 44 of 47 normal human chromosomes and in all five chimpanzees examined. In contrast, no CAT interruptions were found in Old World monkeys or expanded human alleles. The number and positions of CAT interruptions may be important in stabilizing CAG repeat tracts in normal chromosomes. At least five codons occupy the region corresponding to the polyglutamine tract at the SCA1 locus in mice, rats, and other rodents. They comprise three or four CCN (coding for proline) in addition to one or two CAG repeats. Am. J. Med. Genet. 74:488–493, 1997. © 1997 Wiley-Liss, Inc. 相似文献
4.
Gao R Matsuura T Coolbaugh M Zühlke C Nakamura K Rasmussen A Siciliano MJ Ashizawa T Lin X 《European journal of human genetics : EJHG》2008,16(2):215-222
Trinucleotide repeat expansions are dynamic mutations causing many neurological disorders, and their instability is influenced by multiple factors. Repeat configuration seems particularly important, and pure repeats are thought to be more unstable than interrupted repeats. But direct evidence is still lacking. Here, we presented strong support for this hypothesis from our studies on spinocerebellar ataxia type 17 (SCA17). SCA17 is a typical polyglutamine disease caused by CAG repeat expansion in TBP (TATA binding protein), and is unique in that the pure expanded polyglutamine tract is coded by either a simple configuration with long stretches of pure CAGs or a complex configuration containing CAA interruptions. By small pool PCR (SP-PCR) analysis of blood DNA from SCA17 patients of distinct racial backgrounds, we quantitatively assessed the instability of these two types of expanded alleles coding similar length of polyglutamine expansion. Mutation frequency in patients harboring pure CAG repeats is 2-3 folds of those with CAA interruptions. Interestingly, the pure CAG repeats showed both expansion and deletion while the interrupted repeats exhibited mostly deletion at a significantly lower frequency. These data strongly suggest that repeat configuration is a critical determinant for instability, and CAA interruptions might serve as a limiting element for further expansion of CAG repeats in SCA17 locus, suggesting a molecular basis for lack of anticipation in SCA17 families with interrupted CAG expansion. 相似文献
5.
Lin JX Ishikawa K Sakamoto M Tsunemi T Ishiguro T Amino T Toru S Kondo I Mizusawa H 《Journal of human genetics》2008,53(4):287-295
Spinocerebellar ataxia type 1 (SCA1; OMIM: #164400) is an autosomal dominant cerebellar ataxia caused by an expansion of CAG
repeat, which encodes polyglutamine, in the ataxin-1 (ATXN1) gene. Length of polyglutamine in the ATXN1 protein is the critical determinant of pathogenesis of this disease. Molecular
diagnosis of SCA1 is usually undertaken by assessing the length of CAG repeat configuration using primers spanning this configuration.
However, this conventional method may potentially lead to misdiagnosis in assessing polyglutamine-encoding CAG repeat length,
since CAT interruptions may be present within the CAG repeat configuration, not only in normal controls but also in neurologically
symptomatic subjects. We developed a new method for assessing actual CAG repeat numbers not interrupted by CAT sequences.
Polymerase chain reaction using a primer pair labeled with two different fluorescences followed by restriction enzyme digestion
with SfaNI which recognizes the sequence “GCATC(N)5”, lengths of actual CAG repeats that encode polyglutamine were directly detected. We named this method “dual fluorescence labeled PCR-restriction fragment length analysis”. We found that numbers of actual CAG repeat encoding polyglutamine do not overlap between our cohorts of normal chromosomes
(n = 385) and SCA1 chromosomes (n = 5). We conclude that the present method is a useful way for molecular diagnosis of SCA1.
Analysis of CAG repeats in the ataxin-1 gene. 相似文献
6.
We screened a cohort of 181 patients with features of primary progressive ataxia and chorea for spinocerebellar ataxias 17 (SCA17) mutation after excluding other known SCAs, Huntington's disease (HD), dentatorubral-pallidoluysian atrophy (DRPLA), and non-genetic causes. This study included patients with known family history of SCA, those with sporadic onset and cases of uncertain family history. Two unrelated patients with Huntington's disease-like phenotype and cerebellar signs are described with homozygous expansions of 47 and 48 CAG/CAA repeats. A family member with early signs of ataxia was found to carry 37 and 48 repeats. There were fewer CAA interruptions in the repeat sequences of patients than in the controls. The normal repeat range in controls was 21-42, with 91% of the alleles located between 33 and 39 repeats. This is the first report of rare homozygous SCA17 mutation in Indian patients presenting with HD-like phenotype. 相似文献
7.
东北地区正常汉族人群 SCA1及 SCA3/MJD基因内CAG重复变异研究 总被引:3,自引:1,他引:3
目的 对东北地区 110名汉族正常人 SCA1及 SCA3/ MJD基因 (CAG) n拷贝进行检测 ,探讨其正常变异范围 ,并对临床诊断为遗传型脊髓小脑共济失调的 8个家系的 2 5例患者和 6个散发病例进行基因分型评价和症状前及产前诊断。方法 应用荧光 - PCR方法测定不同基因型片段长度 ,并进行 DNA序列分析。结果 SCA3/ MJD基因 (CAG) n正常变异范围为 14~ 38个拷贝 ,集中于 14个拷贝 ,其等位基因频率为 39.5 5 % ,杂合频率为 78.18% ,共 13种等位基因。检出一个家系先证者携带有 (CAG) 6 8的 SCA3/ MJD基因 ,并对该家系成员进行了症状前诊断 ,没有发现 (CAG) n拷贝异常突变 ;SCA1基因内 (CAG) n正常变异范围 2 0~ 39拷贝 ,集中于 2 6及 2 7次 ,等位基因频率分别为 34.0 9%和 2 0 .91% ,杂合频率为 84 .5 5 % ,共 13种等位基因 ;散发病例未检出 CAG扩展性突变。结论 SCA1及 SCA3/ MJD基因中 (CAG) n正常变异范围存在地区和种族差异 ,SCAs基因分型是该病症状前及产前诊断的首选策略。 相似文献
8.
I. Silveira P. Coutinho P. Maciel C. Gaspar S. Hayes A. Dias J. Guimares L. Loureiro J. Sequeiros G.A. Rouleau 《American journal of medical genetics. Part A》1998,81(2):134-138
The spinocerebellar ataxias (SCAs) are clinically and genetically a heterogeneous group of neurodegenerative disorders. To date, eight different loci causing SCA have been identified: SCA1, SCA2, Machado-Joseph disease (MJD)/SCA3, SCA4, SCA5, SCA6, SCA7, and dentatorubropallidoluysian atrophy (DRPLA). Expansion of a CAG repeat in the disease genes has been found in five of these disorders. To estimate the relative frequencies of the SCA1, DRPLA, MJD, SCA2, and SCA6 mutations among Portuguese ataxia patients, we collected DNA samples from 48 ataxia families and performed polymerase chain reaction (PCR) amplification of the CAG repeat mutations on chromosomes 6p, 12p, 14q, 12q, and 19p, respectively. Fifty-five individuals belonging to 34 dominant families (74%) had an expanded CAG repeat at the MJD gene. In five individuals from two kindreds with a dominant pattern of inheritance (4%), an expanded CAG repeat at the SCA2 gene was found. In MJD patients, the normal allele size ranged from 13 to 41, whereas the mutant alleles contained 65 to 80 repeats. For the SCA2 patients, normal alleles had 22 or 23, while expanded alleles had between 36 and 47 CAG units. We did not find the SCA1, DRPLA, or SCA6 mutations in our group of families. The MJD mutation remains the most common cause of SCA in Portugal, while a small number of cases are caused by mutations at the SCA2 gene, and 22% are due to still unidentified genes. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 81:134–138, 1998. © 1998 Wiley-Liss, Inc. 相似文献
9.
脊髓小脑共济失调患者CAG病理重复次数检测 总被引:5,自引:3,他引:2
目的 研究中国汉族人群脊髓小脑性共济失调(spinocerebellar ataxia,SCA)1、2、3、6、7、12、17亚型致病基因的CAG三核苷酸病理重复次数范围.方法 应用聚合酶链反应、琼脂糖凝胶电泳、T载体克隆重组DNA技术并结合直接测序等技术对559例临床诊断为SCA的患者(363例常染色体显性遗传先证者,196例散发患者)进行SCA1、SCA2、SCA3/马查多-约瑟夫病(Machado-Joseph disease,MJD)、SCA6、SCA7、SCA12和SCA17致病基因CAG三核苷酸病理重复次数突变分析.结果 在559例SCA患者中,共检测出SCA1患者23例,CAG病理重复次数范围39~60次,平均(51.09±4.88)次;SCA2患者32例,CAG病理重复次数范围36~51次,平均(40.34±4.40)次;SCA3/MJD患者305例,CAG病理重复次数范围49~86次,平均(73.84±5.07)次;SCA6患者9例,CAG病理重复次数范围23~29次,平均(25.56±1.94)次;SCA7患者27例,CAG病理重复次数范围38~71次,平均(58.22±10.90)次;SCA12患者3例,CAG病理重复次数范围51~52次,平均(51.33±0.58)次;SCA17患者2例,CAG病理重复次数范围53~55次,平均(54.00±1.41)次.结论 SCA1的39次CAG病理重复、SCA3/MJD的49次CAG病理重复和SCA12的51次CAG病理重复为国内或国外报道的最小CAG病理重复次数;SCA3/MJD的86次CAG病理重复为国内外报道的最大CAG病理重复次数;SCA17为国内首次发现的SCA亚型;首次建立中国汉族人群不同SCA亚型CAG三核苷酸病理重复次数范围标准. 相似文献
10.
Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32 families 总被引:5,自引:6,他引:5
Cancel G; Durr A; Didierjean O; Imbert G; Burk K; Lezin A; Belal S; Benomar A; Abada-Bendib M; Vial C; Guimaraes J; Chneiweiss H; Stevanin G; Yvert G; Abbas N; Saudou F; Lebre AS; Yahyaoui M; Hentati F; Vernant JC; Klockgether T; Mandel JL; Agid Y; Brice A 《Human molecular genetics》1997,6(5):709-715
Spinocerebellar ataxia 2 (SCA2) is caused by the expansion of an unstable
CAG repeat encoding a polyglutamine tract. One hundred and eighty four
index patients with autosomal dominant cerebellar ataxia type I were
screened for this mutation. We found expansion in 109 patients from 30
families of different geographical origins (15%) and in two isolated cases
with no known family histories (2%). The SCA2 chromosomes contained from 34
to 57 repeats and consisted of a pure stretch of CAG, whereas all tested
normal chromosomes (14-31 repeats), except one with 14 repeats, were
interrupted by 1-3 repeats of CAA. As in other diseases caused by unstable
mutations, a strong negative correlation was observed between the age at
onset and the size of the CAG repeat (r = -0.81). The frequency of several
clinical signs such as myoclonus, dystonia and myokymia increased with the
number of CAG repeats whereas the frequency of others was related to
disease duration. The CAG repeat was highly unstable during transmission
with variations ranging from -8 to +12, and a mean increase of +2.2, but
there was no significant difference according to the parental sex. This
instability was confirmed by the high degree of gonadal mosaicism observed
in sperm DNA of one patient.
相似文献
11.
12.
Matsuyama Z; Kawakami H; Maruyama H; Izumi Y; Komure O; Udaka F; Kameyama M; Nishio T; Kuroda Y; Nishimura M; Nakamura S 《Human molecular genetics》1997,6(8):1283-1287
Spinocerebellar ataxia 6 (SCA6) is an autosomal dominant spinocerebellar
degeneration caused by the expansion of the polymorphic CAG repeat in the
human alpha1A voltage-dependent calcium channel subunit gene (CACNL1A4
gene). We have analyzed 60 SCA6 individuals from 39 independent SCA6
Japanese families and found that the CAG repeat length is inversely
correlated with the age of onset (n = 58, r = - 0.51, P < 0.0001). SCA6
chromosomes contained 21-30 repeat units, whereas normal chromosomes
displayed 6-17 repeats. There was no overlap between the normal and
affected CAG repeat number. The anticipation of the disease was observed
clinically in all eight parent-child pairs that we examined; the mean age
of onset was significantly lower (P = 0.0042) in children than in parents.
However, a parent-child analysis showed the increase in the expansion of
CAG repeats only in one pair and no diminution in any affected cases. This
result suggests that factors other than CAG repeats may produce the
clinical anticipation. A homozygotic case could not demonstrate an
unequivocal gene dosage effect on the age of onset.
相似文献
13.
14.
Population variation analysis at nine loci containing expressed trinucleotide repeats 总被引:1,自引:0,他引:1
C. JODICE B. GIOVANNONE V. CALABRESI M. BELLOCCHI L. TERRENATO A. NOVELLETTO 《Annals of human genetics》1997,61(5):425-438
The polymorphisms of nine loci containing reiterated CAG repeats were examined in four populations from three continents. Their normal variation was analysed across populations or in subsets of loci grouped according to either the presence/absence of disease-associated expansions or CAG interruptions. A unifying feature of the allele distributions of all loci in all populations was the marked non-normality. Significantly larger numbers of alleles, average lengths, length ranges and variances in repeat number were observed in loci with vs. without known expansions. Significantly longer alleles were found at loci with vs. without interruption of the (CAG)n motif. The nine loci detected levels of inter-population variability comparable to other loci. Altogether the data are at odds with a model assuming that autosomal expressed trinucleotides accumulate variation exclusively by insertion/deletion of a single unit. 相似文献
15.
Matilla T.; Volpinl V.; Genis D.; Rosell J.; Corral J.; Davalos A.; Molins A.; Estivill X. 《Human molecular genetics》1993,2(12):2123-2128
Autosomal dominant cerebellar ataxia type 1 (ADCA1) is a clinicaland genetic heterogeneous neurodegenerative disorder which leadsto progressive cerebellar ataxia. One defective gene responsiblefor the disease was first localised to 6p (SCA1, splnocerebellarataxia type 1) and the mutation has been more recently characterised.We have analysed the CAG-repeat mutation responsible for theSCA1 phenotype in a large Spanish kindred with 41 affected members,in which positive linkage with D6S89 was previously shown. All(10) clinically affected members analysed were heterozygouswith one disease allele being between 41 to 57 CAG repeats,and the other in the normal range, from 6 to 39 repeats. Nineclinically unaffected individuals who were between the agesof 18 and 40, were found to have expansions of the CAG repeat(41 to 59), and 22 other at risk individuals werefound to have inherited the SCA1 gene with copies of the CAGrepeat in the normal range. We have also observed that affectedfathers passed on the mutated SCA1 gene with larger increasesin the number of CAG repeats than affected mothers did. In onecase a decrease in the number of CAG repeats (51 to 50) wasdetected in the transmission from the affected mother, and intwo cases no change was observed in the transmission of a 41allele repeat by a mother. As in the other disorders in whichknowledge of the mutation has been obtained, analysis of therepeat expansion dramatically changes diagnosis of SCA1. 相似文献
16.
Molecular and clinical correlations in autosomal dominant cerebellar ataxia with progressive macular dystrophy (SCA7) 总被引:11,自引:4,他引:11
David G; Durr A; Stevanin G; Cancel G; Abbas N; Benomar A; Belal S; Lebre AS; Abada-Bendib M; Grid D; Holmberg M; Yahyaoui M; Hentati F; Chkili T; Agid Y; Brice A 《Human molecular genetics》1998,7(2):165-170
Spinocerebellar ataxia 7 (SCA7) is caused by the expansion of an unstable
CAG repeat in the first exon of the SCA7 gene. We have analyzed the SCA7
mutation in 19 families and one isolated case of various geographical
origins, presenting with autosomal dominant cerebellar ataxia with
progressive macular dystrophy. The SCA7 CAG repeat was expanded in 77
patients and in 11 at-risk individuals, with alleles containing from 37 to
130 repeats, demonstrating that SCA7 is genetically homogeneous. Repeats on
normal alleles contained from 7 to 35 CAGs. There was a strong negative
correlation (r = -0.84) between the age at onset and the size of the CAG
repeat expansion in SCA7 patients. Larger expansions were associated with
earlier onset, a more severe and rapid clinical course, and a higher
frequency of decreased vision, ophthalmoplegia, extensor plantar response
and scoliosis. The frequency of other clinical signs such as dysphagia and
sphincter disturbances increased with disease duration. The mutation was
highly unstable during transmission, with a mean increase of 10 +/- 16 CAG
repeats, which was significantly greater in paternal (15 +/- 20) than in
maternal (5 +/- 5) transmissions. This correlated well with the marked
anticipation (19 +/- 13 years) observed in the families. Gonadal mosaicism,
observed in the sperm of a patient, was particularly important, with
expanded alleles ranging from 42 to >155 CAG repeats. The degree of
instability during transmission, resulting mostly in expansions, is greater
than in the seven other neurodegenerative disorders caused by polyglutamine
expansions.
相似文献
17.
SCA6 is caused by moderate CAG expansion in the alpha1A-voltage- dependent calcium channel gene 总被引:1,自引:3,他引:1
Riess O; Schols L; Bottger H; Nolte D; Vieira-Saecker AM; Schimming C; Kreuz F; Macek M Jr; Krebsova A; Macek M Sen; Klockgether T; Zuhlke C; Laccone FA 《Human molecular genetics》1997,6(8):1289-1293
Recently, moderate (CAG)>20 repeat expansions in the alpha1A-voltage-
dependent calcium channel gene (CACNL1A4) have been identified in a
previously unmapped type of SCA which has been named SCA6. We investigated
the (CAG)n repeat length of the CACNL1A4 gene in 733 patients with sporadic
ataxia and in 46 German families with dominantly inherited SCA which do not
harbor the SCA1, SCA2, or MJD1/SCA3 mutation, respectively. The SCA6 (CAG)n
expansion was identified in 32 patients most frequently with late
manifestation of the disease. The (CAG)n stretch of the affected allele
varied between 22 and 28 trinucleotide units and is therefore the shortest
trinucleotide repeat expansion causing spinocerebellar ataxia. The (CAG)n
repeat length is inversely correlated with the age at onset. In 11 parental
transmissions of the expanded allele no repeat instability has been
observed. Repeat instability was also not found for the normal allele
investigating 431 meioses in the CEPH families. Analyzing 248 apparently
healthy octogenerians revealed one allele of 18 repeats which is the
longest normal CAG repeat in the CACNL1A4 gene reported. The SCA6 mutation
causes the disease in approximately 10% of autosomal dominant SCA in
Germany. Most importantly, the trinucleotide expansion was observed in four
ataxia patients without obvious family history of the disease which
necessitates a search for the SCA6 (CAG)n expansion even in sporadic
patients.
相似文献
18.
Takiyama Y; Sakoe K; Soutome M; Namekawa M; Ogawa T; Nakano I; Igarashi S; Oyake M; Tanaka H; Tsuji S; Nishizawa M 《Human molecular genetics》1997,6(7):1063-1068
To investigate the mechanism of the meiotic instability of expanded CAG
repeats in the gene for Machado-Joseph disease (MJD1), we analyzed the CAG
repeat sizes of 1036 single sperm from six individuals with Machado- Joseph
disease (MJD). The segregation ratio between single sperm with an expanded
allele and those with a normal allele is significantly different (P
<0.0001) from the expected 1:1 segregation ratio, which demonstrates
segregation distortion of expanded alleles in male meiosis. In single sperm
from individuals with the [expanded (CAG)n- CGG]/[normal (CAG)n-GGG]
genotype, significantly greater instability of the CAG repeat was observed
compared with single sperm from individuals with the [expanded
(CAG)n-CGG]/[normal (CAG)n-CGG] genotype (F-test, P <0.001). These
findings in single sperm confirm non-Mendelian transmission of the MJD1
gene and the effect of the intragenic CGG/GGG polymorphism on the
intergenerational instability of the CAG repeats in the MJD1 gene, which
have been observed in clinical and genetic studies. Our results indicate
similarities and dissimilarities between MJD and Huntington's disease or
myotonic dystrophy in terms of the inter-allelic interaction, segregation
distortions and size distribution of trinucleotide repeats in mutant
alleles. Further study is required to determine whether there is a common
mechanism underlying the instability of the triplet repeats in 'triplet
repeat diseases'.
相似文献
19.
Analysis of spinocerebellar ataxia type 2 gene and haplotype analysis: (CCG)1-2 polymorphism and contribution to founder effect
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Mizushima K Watanabe M Kondo I Okamoto K Shizuka M Abe K Aoki M Shoji M 《Journal of medical genetics》1999,36(2):112-114
Spinocerebellar ataxia type 2 is a familial spinocerebellar ataxia with autosomal dominant inheritance. The gene responsible was recently cloned and this disorder was found to be the result of a CAG expansion in its open reading frame. We analysed 13 SCA2 patients in seven unrelated families in Gunma Prefecture, Japan. In four of the seven families, we detected CCG or CCGCCG interruptions in only the expanded alleles. Cosegregation of these polymorphisms with SCA2 patients was established within each family. Together with the results of haplotype analyses, we considered that at least two founders were present in our area and that these (CCG)1-2 polymorphisms may make analysis of founder effects easier. By sequencing analysis we found that although the number of the long CAG repeat varied in each subclone of expanded alleles, these polymorphisms did not change their configuration. This finding suggests that CCG or CCGCCG sequences are stable when surrounded by the long CAG repeat and a single CAG. Moreover, the presence of these polymorphisms may lead to miscounting the repeat size by conventional estimation using a size marker such as an M13 sequencing ladder. Therefore we should consider these polymorphisms and accurately determine the repeat size by sequencing. 相似文献
20.
Yoshihiro Suzuki Hidenao Sasaki Akemi Wakisaka Akio Takada Takashi Yoshiki Kiyoshi Iwabuchi Kunio Tashiro Toshiyuki Fukazawa Takeshi Hamada 《Journal of human genetics》1995,40(1):131-143
Summary SCA1 is caused by expansion of an unstable CAG triplet repeat in a novel gene located on the short arm of chromosome 6. In 126 Japanese individuals from 12 pedigrees with SCA1, studies were done to determine if they carried this mutant gene. All the affected and presymptomatic individuals, determined by haplotype segregation analyses, carried an abnormally expanded allele with the range of 39–63 repeat units. This repeat size inversely correlated with the age at onset. However, contrary to reported results, size of the repeat did not correlate with gender of the transmitting parent. Therefore, the CAG triplet repeat instability on paternal transmission is not likely to be fundamental to SCA1. 相似文献