当前位置： SCI文献检索 > AMERICAN JOURNAL OF HUMAN GENETICS期刊下所有文献 > Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes.

Sex-dependent mechanisms for expansions and contractions of the CAG repeat on affected Huntington disease chromosomes.

Abstract：

:A total of 254 affected parent-child pairs with Huntington disease (HD) and 440 parent-child pairs with CAG size in the normal range were assessed to determine the nature and frequency of intergenerational CAG changes in the HD gene. Intergenerational CAG changes are extremely rare (3/440 [0.68%]) on normal chromosomes. In contrast, on HD chromosomes, changes in CAG size occur in approximately 70% of meioses on HD chromosomes, with expansions accounting for 73% of these changes. These intergenerational CAG changes make a significant but minor contribution to changes in age at onset (r2 = .19). The size of the CAG repeat influenced larger intergenerational expansions (> 7 CAG repeats), but the likelihood of smaller expansions or contractions was not influenced by CAG size. Large expansions (> 7 CAG repeats) occur almost exclusively through paternal transmission (0.96%; P < 10(-7)), while offspring of affected mothers are more likely to show no change (P = .01) or contractions in CAG size (P = .002). This study demonstrates that sex of the transmitting parent is the major determinant for CAG intergenerational changes in the HD gene. Similar paternal sex effects are seen in the evolution of new mutations for HD from intermediate alleles and for large expansions on affected chromosomes. Affected mothers almost never transmit a significantly expanded CAG repeat, despite the fact that many have similar large-sized alleles, compared with affected fathers. The sex-dependent effects of major expansion and contractions of the CAG repeat in the HD gene implicate different effects of gametogenesis, in males versus females, on intergenerational CAG repeat stability.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Kremer B,Almqvist E,Theilmann J,Spence N,Telenius H,Goldberg YP,Hayden MR

subject

Has Abstract

pub_date

1995-08-01 00:00:00

pages

343-50

issue

2

eissn

0002-9297

issn

1537-6605

journal_volume

57

pub_type

杂志文章

相关文献

AMERICAN JOURNAL OF HUMAN GENETICS文献大全
  • Geographically separate increases in the frequency of the derived ADH1B*47His allele in eastern and western Asia.

    abstract：:The ADH1B Arg47His polymorphism has been convincingly associated with alcoholism in numerous studies of several populations in Asia and Europe. In a review of literature from the past 30 years, we have identified studies that report allele frequencies of this polymorphism for 131 population samples from many different...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/521201

    authors： Li H,Mukherjee N,Soundararajan U,Tarnok Z,Barta C,Khaliq S,Mohyuddin A,Kajuna SL,Mehdi SQ,Kidd JR,Kidd KK

    更新日期：2007-10-01 00:00:00

  • Genomewide linkage analysis identifies polymorphism in the human interferon-gamma receptor affecting Helicobacter pylori infection.

    abstract：:Helicobacter pylori is considered the most prevalent infectious agent among humans, and it causes gastric inflammation, gastroduodenal ulcers, and a risk of gastric cancer. We performed a genomewide linkage analysis among Senegalese siblings phenotyped for H. pylori-reactive serum immunoglobulin G. A multipoint LOD sc...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/367714

    authors： Thye T,Burchard GD,Nilius M,Müller-Myhsok B,Horstmann RD

    更新日期：2003-02-01 00:00:00

  • A common ancestral origin of the frequent and widespread 2299delG USH2A mutation.

    abstract：:Usher syndrome type IIa is an autosomal recessive disorder characterized by mild-to-severe hearing loss and progressive visual loss due to retinitis pigmentosa. The mutation that most commonly causes Usher syndrome type IIa is a 1-bp deletion, described as "2299delG," in the USH2A gene. The mutation has been identifie...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/321269

    authors： Dreyer B,Tranebjaerg L,Brox V,Rosenberg T,Möller C,Beneyto M,Weston MD,Kimberling WJ,Cremers CW,Liu XZ,Nilssen O

    更新日期：2001-07-01 00:00:00

  • Chromosome breakage in the Prader-Willi and Angelman syndromes involves recombination between large, transcribed repeats at proximal and distal breakpoints.

    abstract：:Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are distinct neurobehavioral disorders that most often arise from a 4-Mb deletion of chromosome 15q11-q13 during paternal or maternal gametogenesis, respectively. At a de novo frequency of approximately.67-1/10,000 births, these deletions represent a common struct...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/302510

    authors： Amos-Landgraf JM,Ji Y,Gottlieb W,Depinet T,Wandstrat AE,Cassidy SB,Driscoll DJ,Rogan PK,Schwartz S,Nicholls RD

    更新日期：1999-08-01 00:00:00

  • Mutations in the SPARC-related modular calcium-binding protein 1 gene, SMOC1, cause waardenburg anophthalmia syndrome.

    abstract：:Waardenburg anophthalmia syndrome, also known as microphthalmia with limb anomalies, ophthalmoacromelic syndrome, and anophthalmia-syndactyly, is a rare autosomal-recessive developmental disorder that has been mapped to 10p11.23. Here we show that this disease is heterogeneous by reporting on a consanguineous family, ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2010.12.002

    authors： Abouzeid H,Boisset G,Favez T,Youssef M,Marzouk I,Shakankiry N,Bayoumi N,Descombes P,Agosti C,Munier FL,Schorderet DF

    更新日期：2011-01-07 00:00:00

  • Contrasting linkage-disequilibrium patterns between cases and controls as a novel association-mapping method.

    abstract：:Identification and description of genetic variation underlying disease susceptibility, efficacy, and adverse reactions to drugs remains a difficult problem. One of the important steps in the analysis of variation in a candidate region is the characterization of linkage disequilibrium (LD). In a region of genetic assoc...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/503710

    authors： Zaykin DV,Meng Z,Ehm MG

    更新日期：2006-05-01 00:00:00

  • Allele-specific replication of 15q11-q13 loci: a diagnostic test for detection of uniparental disomy.

    abstract：:Allele-specific replication differences have been observed in imprinted chromosomal regions. We have exploited this characteristic of an imprinted region by using FISH at D15S9 and SNRPN (small nuclear ribonucleo protein N) on interphase nuclei to distinguish between Angelman and Prader-Willi syndrome patient samples ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： White LM,Rogan PK,Nicholls RD,Wu BL,Korf B,Knoll JH

    更新日期：1996-08-01 00:00:00

  • Effective gene therapy of mice with congenital erythropoietic porphyria is facilitated by a survival advantage of corrected erythroid cells.

    abstract：:Achieving long-term expression of a therapeutic gene in a given hematopoietic lineage remains an important goal of gene therapy. Congenital erythropoietic porphyria (CEP) is a severe autosomal-recessive disorder characterized by a deficiency in uroporphyrinogen III synthase (UROS), the fourth enzyme of the heme biosyn...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2007.09.007

    authors： Robert-Richard E,Moreau-Gaudry F,Lalanne M,Lamrissi-Garcia I,Cario-André M,Guyonnet-Dupérat V,Taine L,Ged C,de Verneuil H

    更新日期：2008-01-01 00:00:00

  • The tyrosinase-positive oculocutaneous albinism gene shows locus homogeneity on chromosome 15q11-q13 and evidence of multiple mutations in southern African negroids.

    abstract：:Tyrosinase-positive oculocutaneous albinism (ty-pos OCA) is an autosomal recessive disorder of the melanin pigmentary system. South African ty-pos OCA individuals occur with two distinct phenotypes, with or without darkly pigmented patches (ephelides, or dendritic freckles) on exposed areas of the skin. These phenotyp...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Kedda MA,Stevens G,Manga P,Viljoen C,Jenkins T,Ramsay M

    更新日期：1994-06-01 00:00:00

  • Parental somatic mosaicism is underrecognized and influences recurrence risk of genomic disorders.

    abstract：:New human mutations are thought to originate in germ cells, thus making a recurrence of the same mutation in a sibling exceedingly rare. However, increasing sensitivity of genomic technologies has anecdotally revealed mosaicism for mutations in somatic tissues of apparently healthy parents. Such somatically mosaic par...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2014.07.003

    authors： Campbell IM,Yuan B,Robberecht C,Pfundt R,Szafranski P,McEntagart ME,Nagamani SC,Erez A,Bartnik M,Wiśniowiecka-Kowalnik B,Plunkett KS,Pursley AN,Kang SH,Bi W,Lalani SR,Bacino CA,Vast M,Marks K,Patton M,Olofsson P,P

    更新日期：2014-08-07 00:00:00

  • Evidence that specific mtDNA point mutations may not accumulate in skeletal muscle during normal human aging.

    abstract：:It is unclear at present whether specific mtDNA point mutations accumulate during normal human aging. In order to address this question, we used quantitative PCR of total DNA isolated from skeletal muscle from normal individuals of various ages to search for the presence and amount of spontaneous mtDNA point mutations...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Pallotti F,Chen X,Bonilla E,Schon EA

    更新日期：1996-09-01 00:00:00

  • A higher mutational burden in females supports a "female protective model" in neurodevelopmental disorders.

    abstract：:Increased male prevalence has been repeatedly reported in several neurodevelopmental disorders (NDs), leading to the concept of a "female protective model." We investigated the molecular basis of this sex-based difference in liability and demonstrated an excess of deleterious autosomal copy-number variants (CNVs) in f...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2014.02.001

    authors： Jacquemont S,Coe BP,Hersch M,Duyzend MH,Krumm N,Bergmann S,Beckmann JS,Rosenfeld JA,Eichler EE

    更新日期：2014-03-06 00:00:00

  • A genomewide screen for late-onset Alzheimer disease in a genetically isolated Dutch population.

    abstract：:Alzheimer disease (AD) is the most common cause of dementia. We conducted a genome screen of 103 patients with late-onset AD who were ascertained as part of the Genetic Research in Isolated Populations (GRIP) program that is conducted in a recently isolated population from the southwestern area of The Netherlands. All...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/518720

    authors： Liu F,Arias-Vásquez A,Sleegers K,Aulchenko YS,Kayser M,Sanchez-Juan P,Feng BJ,Bertoli-Avella AM,van Swieten J,Axenovich TI,Heutink P,van Broeckhoven C,Oostra BA,van Duijn CM

    更新日期：2007-07-01 00:00:00

  • Replication of autism linkage: fine-mapping peak at 17q21.

    abstract：:Autism is a heritable but genetically complex disorder characterized by deficits in language and in reciprocal social interactions, combined with repetitive and stereotypic behaviors. As with many genetically complex disorders, numerous genome scans reveal inconsistent results. A genome scan of 345 families from the A...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/430278

    authors： Cantor RM,Kono N,Duvall JA,Alvarez-Retuerto A,Stone JL,Alarcón M,Nelson SF,Geschwind DH

    更新日期：2005-06-01 00:00:00

  • De novo myotonic dystrophy mutation in a Nigerian kindred.

    abstract：:An expansion of an unstable (CTG)n trinucleotide repeat in the 3' UTR of a gene encoding a putative serine/threonine protein kinase (DMPK) on human chromosome 19q13.3 has been shown to be specific for the myotonic dystrophy (DM) disease phenotype. In addition, a single haplotype composed of nine alleles within and fla...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Krahe R,Eckhart M,Ogunniyi AO,Osuntokun BO,Siciliano MJ,Ashizawa T

    更新日期：1995-05-01 00:00:00

  • A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus.

    abstract：:Dopamine-beta-hydroxylase (D beta H) catalyzes the conversion of dopamine to norepinephrine and is released from sympathetic neurons into the circulation. Plasma-D beta H activity varies widely between individuals, and a subgroup of the population has very low activity levels. Mounting evidence suggests that the DBH s...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/318198

    authors： Zabetian CP,Anderson GM,Buxbaum SG,Elston RC,Ichinose H,Nagatsu T,Kim KS,Kim CH,Malison RT,Gelernter J,Cubells JF

    更新日期：2001-02-01 00:00:00

  • Gene mutations in the succinate dehydrogenase subunit SDHB cause susceptibility to familial pheochromocytoma and to familial paraganglioma.

    abstract：:The pheochromocytomas are an important cause of secondary hypertension. Although pheochromocytoma susceptibility may be associated with germline mutations in the tumor-suppressor genes VHL and NF1 and in the proto-oncogene RET, the genetic basis for most cases of nonsyndromic familial pheochromocytoma is unknown. Rece...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/321282

    authors： Astuti D,Latif F,Dallol A,Dahia PL,Douglas F,George E,Sköldberg F,Husebye ES,Eng C,Maher ER

    更新日期：2001-07-01 00:00:00

  • Mutations in ROGDI Cause Kohlschütter-Tönz Syndrome.

    abstract：:Kohlschütter-Tönz syndrome (KTS) is an autosomal-recessive disease characterized by the combination of epilepsy, psychomotor regression, and amelogenesis imperfecta. The molecular basis has not yet been elucidated. Here, we report that KTS is caused by mutations in ROGDI. Using a combination of autozygosity mapping an...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2012.02.012

    authors： Schossig A,Wolf NI,Fischer C,Fischer M,Stocker G,Pabinger S,Dander A,Steiner B,Tönz O,Kotzot D,Haberlandt E,Amberger A,Burwinkel B,Wimmer K,Fauth C,Grond-Ginsbach C,Koch MJ,Deichmann A,von Kalle C,Bartram CR,Kohls

    更新日期：2012-04-06 00:00:00

  • The genetics of sun sensitivity in humans.

    abstract：:Humans vary >100-fold in their sensitivity to the harmful effects of ultraviolet radiation. The main determinants of sensitivity are melanin pigmentation and less-well-characterized differences in skin inflammation and repair processes. Pigmentation has a high heritability, but susceptibility to cancers of the skin, a...

    journal_title：American journal of human genetics

    pub_type： 杂志文章,评审

    doi：10.1086/425285

    authors： Rees JL

    更新日期：2004-11-01 00:00:00

  • Submicroscopic deletions at the WAGR locus, revealed by nonradioactive in situ hybridization.

    abstract：:Fluorescence in situ hybridization (FISH) with biotin-labeled probes mapping to 11p13 has been used for the molecular analysis of deletions of the WAGR (Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation) locus. We have detected a submicroscopic 11p13 deletion in a child with inherited aniridia...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Fantes JA,Bickmore WA,Fletcher JM,Ballesta F,Hanson IM,van Heyningen V

    更新日期：1992-12-01 00:00:00

  • Mutation and haplotype studies of familial Mediterranean fever reveal new ancestral relationships and evidence for a high carrier frequency with reduced penetrance in the Ashkenazi Jewish population.

    abstract：:Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever with serositis or synovitis. The FMF gene (MEFV) was cloned recently, and four missense mutations were identified. Here we present data from non-Ashkenazi Jewish and Arab patients in whom we had not originally found mutations...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/302327

    authors： Aksentijevich I,Torosyan Y,Samuels J,Centola M,Pras E,Chae JJ,Oddoux C,Wood G,Azzaro MP,Palumbo G,Giustolisi R,Pras M,Ostrer H,Kastner DL

    更新日期：1999-04-01 00:00:00

  • Familial infantile convulsions and paroxysmal choreoathetosis: a new neurological syndrome linked to the pericentromeric region of human chromosome 16.

    abstract：:Benign infantile familial convulsions is an autosomal dominant disorder characterized by nonfebrile seizures, with the first attack occurring at age 3-12 mo. It is one of the rare forms of epilepsy that are inherited as monogenic Mendelian traits, thus providing a powerful tool for mapping genes involved in epileptic ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/514877

    authors： Szepetowski P,Rochette J,Berquin P,Piussan C,Lathrop GM,Monaco AP

    更新日期：1997-10-01 00:00:00

  • Association and linkage of the dopamine transporter gene and attention-deficit hyperactivity disorder in children: heterogeneity owing to diagnostic subtype and severity.

    abstract：:Attention-deficit hyperactivity disorder (ADHD) affects approximately 3%-5% of children in the United States. In the current psychiatric nomenclature, ADHD comprises three subtypes: inattentive, hyperactive-impulsive, and combined. In this study, we used four analytic strategies to examine the association and linkage ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/302132

    authors： Waldman ID,Rowe DC,Abramowitz A,Kozel ST,Mohr JH,Sherman SL,Cleveland HH,Sanders ML,Gard JM,Stever C

    更新日期：1998-12-01 00:00:00

  • Inferring genetic ancestry: opportunities, challenges, and implications.

    abstract：:Increasing public interest in direct-to-consumer (DTC) genetic ancestry testing has been accompanied by growing concern about issues ranging from the personal and societal implications of the testing to the scientific validity of ancestry inference. The very concept of "ancestry" is subject to misunderstanding in both...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2010.03.011

    authors： Royal CD,Novembre J,Fullerton SM,Goldstein DB,Long JC,Bamshad MJ,Clark AG

    更新日期：2010-05-14 00:00:00

  • Williams syndrome: use of chromosomal microdeletions as a tool to dissect cognitive and physical phenotypes.

    abstract：:In Williams syndrome (WS), a deletion of approximately 1.5 Mb on one copy of chromosome 7 causes specific physical, cognitive, and behavioral abnormalities. Molecular dissection of the phenotype may be a route to identification of genes important in human cognition and behavior. Among the genes known to be deleted in ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/302214

    authors： Tassabehji M,Metcalfe K,Karmiloff-Smith A,Carette MJ,Grant J,Dennis N,Reardon W,Splitt M,Read AP,Donnai D

    更新日期：1999-01-01 00:00:00

  • A mutation in PNPT1, encoding mitochondrial-RNA-import protein PNPase, causes hereditary hearing loss.

    abstract：:A subset of nuclear-encoded RNAs has to be imported into mitochondria for the proper replication and transcription of the mitochondrial genome and, hence, for proper mitochondrial function. Polynucleotide phosphorylase (PNPase or PNPT1) is one of the very few components known to be involved in this poorly characterize...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1016/j.ajhg.2012.09.002

    authors： von Ameln S,Wang G,Boulouiz R,Rutherford MA,Smith GM,Li Y,Pogoda HM,Nürnberg G,Stiller B,Volk AE,Borck G,Hong JS,Goodyear RJ,Abidi O,Nürnberg P,Hofmann K,Richardson GP,Hammerschmidt M,Moser T,Wollnik B,Koehler CM

    更新日期：2012-11-02 00:00:00

  • Mapping of Alport syndrome to the long arm of the X chromosome.

    abstract：:Five X-chromosome DNA markers were typed on 261 members of three large kindreds with Alport syndrome (hereditary glomerulonephritis). Lod scores greater than 3.0 for linkage between the disease locus and two of the markers confirmed X-linked inheritance of the disease. A decreasing gradient in the estimated recombinat...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Atkin CL,Hasstedt SJ,Menlove L,Cannon L,Kirschner N,Schwartz C,Nguyen K,Skolnick M

    更新日期：1988-02-01 00:00:00

  • Origin of the triosephosphate isomerase isozymes in humans: genetic evidence for the expression of a single structural locus.

    abstract：:A genetic approach is used to ascertain that a single structural locus for triosephosphate isomerase (TPI) (E.C.5.3.1.1.) is expressed in rapidly dividing human lymphoblasts. This approach is made possible through the identification of a rare electrophoretic variant of human TPI. The variant phenotype is expressed by ...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Decker RS,Mohrenweiser HW

    更新日期：1981-09-01 00:00:00

  • GDF5 is a second locus for multiple-synostosis syndrome.

    abstract：:Multiple-synostosis syndrome is an autosomal dominant disorder characterized by progressive symphalangism, carpal/tarsal fusions, deafness, and mild facial dysmorphism. Heterozygosity for functional null mutations in the NOGGIN gene has been shown to be responsible for the disorder. However, in a cohort of six proband...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：10.1086/503204

    authors： Dawson K,Seeman P,Sebald E,King L,Edwards M,Williams J 3rd,Mundlos S,Krakow D

    更新日期：2006-04-01 00:00:00

  • X-linked sideroblastic anemia and ataxia: linkage to phosphoglycerate kinase at Xq13.

    abstract：:Molecular linkage analysis was performed on a kindred with X-linked sideroblastic anemia and ataxia. Two-point analysis with a DNA probe for phosphoglycerate kinase (PGK1), which maps to Xq13, suggested linkage to the disorder by a lod score of at least 2.60 at a recombination fraction of zero. The disease in this kin...

    journal_title：American journal of human genetics

    pub_type： 杂志文章

    doi：

    authors： Raskind WH,Wijsman E,Pagon RA,Cox TC,Bawden MJ,May BK,Bird TD

    更新日期：1991-02-01 00:00:00