A new polymerase chain reaction (PCR) assay for the trinucleotide repeat that is unstable and expanded on Huntington's disease chromosomes

Warner, Jon; Barron, Lilias; Brock, D. J. H.

doi:10.1006/mcpr.1993.1034

Cited by 227 publications

(127 citation statements)

References 0 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…The primers used for these assay were: Hu1 5'-ATGAAGGCCTTCGAGTCCCTCAAGTCCTCC-3' and HD3 5'-GGCGGTGGCGGCTGTTGCTGCTGCTGCTGC-3' 22 . These sequences immediately flank the CAG repeat sequence and amplify specifically the CAG repeats, avoiding the downstream CCG polymorphism, and therefore avoiding errors in HD diagnostic test 12 .…”

Section: Methods Methods Methods Methods Methodsmentioning

confidence: 99%

Huntington disease: DNA analysis in brazilian population

Raskin

Allan²,

Teive³

et al. 2000

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

-Huntington disease (HD) is associated with expansions of a CAG trinucleotide repeat in the HD gene. Accurate measurement of a specific CAG repeat sequence in the HD gene in 92 Brazilian controls without HD, 44 Brazilian subjects with clinical findings suggestive of HD and 40 individuals from 6 putative HD families, showed a range from 7 to 33 repeats in normal subjects and 39 to 88 repeats in affected subjects. A trend between early age at onset of first symptoms and increasing number of repeats was seen. Major increase of repeat size through paternal inheritance than through maternal inheritance was observed. Data generated from this study may have significant implications for the etiology, knowledge of the incidence, diagnosis, prognosis, genetic counseling and treatment of HD Brazilian patients.KEY WORDS: Huntington disease, CAG repeats, Brazil, DNA, PCR. Doença de Huntington: análise de DNA na população brasileiraRESUMO -A doença de Huntington (DH) está associada a expansões da seqüência repetitiva de trinucleotídeos CAG no gene HD. Através de análise do número de repetições CAG em indivíduos brasileiros, amostras de 92 indivíduos-controle não afetados pela DH, 44 pacientes com DH e 40 indivíduos de 6 famílias com a DH, demonstrou-se a presença de repetições de 7 até 33 trinucleotídeos CAG nos indivíduos-controle e de 39 até 88 nos alelos mutados dos indivíduos afetados. Foi constatada relação inversa entre a idade de manifestação dos primeiros sintomas da doença e o tamanho do fragmento encontrado. Também foi observado que o número de casos em que ocorrem expansões do trinucleotídeo foi maior quando o pai transmite o alelo mutado do que quando a mãe o transmite. Os dados gerados com este estudo têm importância significativa para a compreensão da etiologia, incidência, diagnóstico, prognóstico e tratamento dos pacientes com DH na população brasileira. O conhecimento da base genética desta doença na população brasileira permitirá um aconselhamento genético mais eficiente às famílias em risco.

show abstract

Section: Methods Methods Methods Methods Methodsmentioning

confidence: 99%

Huntington disease: DNA analysis in brazilian population

Raskin

Allan²,

Teive³

et al. 2000

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

show abstract

“…To determine the precise number of CAG repeats, we used HD1 and HD3 primers, which exclude the adjacent CCG repeat region in the HD gene (Warner et al, 1993). CCG polymorphism analysis was initially performed using primers HD4F and HD5R that span only this repeat region .…”

Section: Dna Analysis Of the Cag And Adjacent Ccg Repeat Regionmentioning

confidence: 99%

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

Hečimović

Klepac

et al. 2002

Hum. Mutat.

View full text Add to dashboard Cite

This study presents the first molecular data on the basis and the origin of Huntington disease in Croatia and is the first such analysis performed among a Slavic population. We analyzed three trinucleotide polymorphisms in the HD gene: CAG, CCG and GAG ∆2642 (E2642del) triplets. Analysis of the CAG repeat size among 44 Huntington patients (39-66 CAGs) and 51 normal individuals (9-34 CAGs) showed that the range of the repeats was similar to previous findings. The frequency of the CCG and ∆2642 polymorphic alleles on N and HD chromosomes was found to correlate well with earlier reports for Western European populations. We found significance for both the CCG7 allele (p=0.004) and the ∆2642 allele (p<0.001) among HD chromosomes. The CCG7 allele was overpresented among affected chromosomes (94.6%), but was also the most frequent CCG allele among normal chromosomes (66.7%). Interestingly, the ∆2642 allele was present on 40.5% HD chromosomes compared to only 9.8% of control chromosomes. Our results indicate that HD mutations in Croatia could be of the same origin as in Western populations and also support the multi-step hypothesis for generating new HD alleles. Similar frequencies and distributions of both the CCG and the ∆2642 polymorphisms in Croatia and Western European normal chromosomes indicate that the prevalence rate of HD in Croatia may be as high as in Western populations. Since we estimated a lower prevalence rate (1 : 100,000), we assume that there are still many misdiagnosed and/or unrecognized cases of Huntington disease in Croatia.

show abstract

“…CAG repeat assays (Warner et al, 1993) were performed on 250 subjects from 65 H D families, some of whom belonged to the above group of families and had agreed to donate blood for research, and the rest ascertained through the request of one member for presymptomatic H D testing. The geographical origins of the latter families were scattered throughout Italy.…”

Section: Hd Familiesmentioning

confidence: 99%

Genetic fitness in Huntington's Disease and Spinocerebellar Ataxia 1: a population genetics model for CAG repeat expansions

Frontali

Sabbadini

Novelletto

et al. 1996

Annals of Human Genetics

View full text Add to dashboard Cite

SUMMARY An analysis of genetic fitness was performed in Huntington's Disease (HD) and Spinocerebellar Ataxia 1 (SCA1) families. Two partially overlapping samples were used: clinically defined HD and SCA1 patients from families ascertained in definite geographical areas, and molecularly typed carriers of HD and SCA1 mutations (CAG trinucleotide expansions). In both cases, a control group of normal relatives was used. HD and SCA1 patients born before 1915–20 had more children than normal controls. Carriers of HD and SCA1 mutations, all in the low/medium expansion range (37–49 and 47–54 CAG repeats respectively), had a higher number of children than controls up to more recent times (1935–1950). The reproduction of heterozygotes for large expansions could be analysed only in subjects born after 1950 and provided indirect evidence of a lower than normal number of children. The above results fit a model based on a differential fitness according to the degree of expansion. Such a model predicts that 1) up to relatively recently the frequency of alleles in the low/medium range has been maintained or even increased by the increased fitness of their carriers, as well as by new mutations, and 2) the frequency of large expansions, part of which are lost at each generation, is maintained through further expansions of alleles in the low/medium expansion range. The implications of such a model on linkage disequilibrium and the possible spread of these diseases in future generations are discussed.

show abstract

A new polymerase chain reaction (PCR) assay for the trinucleotide repeat that is unstable and expanded on Huntington's disease chromosomes

Cited by 227 publications

References 0 publications

Huntington disease: DNA analysis in brazilian population

Huntington disease: DNA analysis in brazilian population

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

Genetic fitness in Huntington's Disease and Spinocerebellar Ataxia 1: a population genetics model for CAG repeat expansions

Contact Info

Product

Resources

About