Abstract:
:X inactivation involves initiation, propagation, and maintenance of genetic inactivation. Studies of replication timing in X;autosome translocations have suggested that X inactivation may spread into adjacent autosomal DNA. To examine the inactivation of autosomal material at the molecular level, we assessed the transcriptional activity of X-linked and autosomal loci spanning an inactive translocation in a phenotypically normal female with a karyotype of 46,X,der(X)t(X;4)(q22;q24). Since 4q duplications usually manifest dysmorphic features and severe growth and mental retardation, the normal phenotype of this individual suggested the spreading of X inactivation throughout the autosomal material. Consistent with this model, reverse transcription-PCR analysis of 20 transcribed sequences spanning 4q24-qter revealed that three known genes and 11 expressed sequence tags (ESTs) were not expressed in a somatic-cell hybrid that carries the translocation chromosome. However, three ESTs and three known genes were expressed from the t(X;4) chromosome and thus "escaped" X inactivation. This direct assay of expression demonstrated that the spreading of inactivation from the adjoining X chromosome was incomplete and noncontiguous. These findings are broadly consistent with the existence of genes known to escape inactivation on normal inactive X chromosomes. However, the fact that a high proportion (30%) of tested autosomal genes escaped inactivation may indicate that autosomal material lacks X chromosome-specific features that are associated with the spreading and/or maintenance of inactivation.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
White WM,Willard HF,Van Dyke DL,Wolff DJdoi
10.1086/301922subject
Has Abstractpub_date
1998-07-01 00:00:00pages
20-8issue
1eissn
0002-9297issn
1537-6605pii
S0002-9297(07)60762-9journal_volume
63pub_type
杂志文章abstract::Many ion channel genes have been associated with human genetic pain disorders. Here we report two large Chinese families with autosomal-dominant episodic pain. We performed a genome-wide linkage scan with microsatellite markers after excluding mutations in three known genes (SCN9A, SCN10A, and TRPA1) that cause simila...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.09.016
更新日期:2013-11-07 00:00:00
abstract::Historical and genetic evidences suggest that the recently founded population of Antioquia (Colombia) is potentially useful for the genetic mapping of complex traits. This population was established in the 16th-17th centuries through the admixture of Amerinds, Europeans, and Africans and grew in relative isolation unt...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/S0002-9297(07)62956-5
更新日期:2000-11-01 00:00:00
abstract::To establish the contribution of germline BRCA1 and BRCA2 mutations to familial ovarian cancer, we have analyzed both genes in DNA samples obtained from an affected individual in each of 112 families containing at least two cases of epithelial ovarian cancer. Germline mutations were found in 43% of the families; BRCA1...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302583
更新日期:1999-10-01 00:00:00
abstract::Hermansky-Pudlak syndrome (HPS) is genetically heterogeneous, and mutations in seven genes have been reported to cause HPS. Autozygosity mapping studies were undertaken in a large consanguineous family with HPS. Affected individuals displayed features of incomplete oculocutaneous albinism and platelet dysfunction. Ski...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/499338
更新日期:2006-01-01 00:00:00
abstract::Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by the formation of cartilage-capped prominences that develop from the growth centers of the long bones. EXT is genetically heterogeneous, with three loci, currently identified on chromosomes 8q24.1, 11p13, and 19q. The EXT1 gene, loca...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1997-01-01 00:00:00
abstract::The level of linkage disequilibrium between the XY275 MspI polymorphism and the X and Y boundaries was investigated in 21 different southern African populations. A full range of frequencies of the high allele was observed on the 1,013 X chromosomes studied, in keeping with published data. In previous studies fixation ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-06-01 00:00:00
abstract::The recent cloning of cDNA encoding the Ca++ release channel (ryanodine receptor) of human sarcoplasmic reticulum has enabled us to use somatic cell hybrids to localize the ryanodine receptor gene (RYR) to the proximal long arm of human chromosome 19. Studies with additional hybrids containing deletions or translocati...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V) are axonal peripheral neuropathies inherited in an autosomal dominant fashion. Our previous genetic and physical mapping efforts localized the responsible gene(s) to a well-defined region on human chromosome 7p. Here, we rep...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/375039
更新日期:2003-05-01 00:00:00
abstract::Using sequence-tagged sites we have performed deletion mapping of the Y chromosome in sex-reversed female patients with a Y chromosome and gonadoblastoma. The GBY gene (gonadoblastoma locus on the Y chromosome) was sublocalized to a small region near the centromere of the Y chromosome. We estimate the size of the GBY ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-12-01 00:00:00
abstract::Although intensive efforts have been undertaken to elucidate the genetic background of immunoglobulin A nephropathy (IgAN), genetic factors associated with the pathogenesis of this disease are still not well understood. We designed a case-control association study that was based on linkage disequilibrium among single-...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/339077
更新日期:2002-03-01 00:00:00
abstract::The first component of the mitochondrial electron-transport chain is especially complex, consisting of 19 nuclear and seven mitochondrion-encoded subunits. Accordingly, a wide range of clinical manifestations are produced by the various mutations occurring in human populations. In this study, we analyze the subunit st...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-06-01 00:00:00
abstract::We report the transmission of HLA haplotypes and Gm allotypes in 97 members of a single kindred containing 257 individuals, 45 of whom were determined by clinical examination, autopsy, or historical data to have had Alzheimer disease (AD). Extensive inbreeding suggests that more than one gene may contribute to suscept...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
abstract::Results are presented on chromosome analyses made on 4,481 embryos or fetuses studied through chorionic villus sampling (CVS) in whom there was no known bias to presence of a chromosome abnormality except advanced parental age. We excluded from the analysis most cases in which mosaicism was diagnosed or in which there...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1988-06-01 00:00:00
abstract::Dyskeratosis congenita (DC) is an inherited disorder characterized by reticular pigmentation of the skin, dystrophic nails, mucosal leukoplakia, and a predisposition to cancer in early adult life. In the majority of cases, DC is an X-linked recessive trait. However, one or more autosomal form(s) of DC may exist. Altho...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::A single base mutation at nucleotide position 3460 (nt 3460) in the ND1 gene in human mtDNA was found to be associated with Leber hereditary optic neuroretinopathy (LHON). The G-to-A mutation converts an alanine to a threonine at the 52d codon of the gene. The mutation also abolishes an AhaII restriction site and thus...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-06-01 00:00:00
abstract::Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders and one of the rare genetic diseases now accessible to therapy. Outside the Ashkenazi Jewish community, a high molecular diversity is observed, leaving approximately 30% of alleles undetected. Nevertheless, very few exhaustive methods have b...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301969
更新日期:1998-08-01 00:00:00
abstract::A family with three children with trisomy 21 in which the mother is a phenotypically normal, trisomy 21/normal mosaic was studied. Chromosome 21 fluorescent heteromorphisms were used to document that two of the three number 21's in two of the Down syndrome offspring were of maternal origin. Five cytogenetic surveys in...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1982-01-01 00:00:00
abstract::Arthrogryposis is a clinical finding that is present either as a feature of a neuromuscular condition or as part of a systemic disease in over 400 Mendelian conditions. The underlying molecular etiology remains largely unknown because of genetic and phenotypic heterogeneity. We applied exome sequencing (ES) in a cohor...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.05.015
更新日期:2019-07-03 00:00:00
abstract::We studied mutations in the mtDNA control region (CR) using deep-rooting French-Canadian pedigrees. In 508 maternal transmissions, we observed four substitutions (0.0079 per generation per 673 bp, 95% CI 0.0023-0.186). Combined with other familial studies, our results add up to 18 substitutions in 1,729 transmissions ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/324024
更新日期:2001-11-01 00:00:00
abstract::The autosomal dominant cerebellar ataxias (ADCA) type I are a group of neurological disorders that are clinically and genetically heterogeneous. Two genes implicated in the disease, SCA1 (spinal cerebellar ataxia 1) and SCA2, are already localized. We have mapped a third locus to chromosome 14q24.3-qter, by linkage an...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-01-01 00:00:00
abstract::Analysis of human-Chinese hamster somatic cell hybrids with spontaneously derived chromosome structural changes has provided data for the regional and subregional localization of gene loci which have previously been assigned to human chromosomes 2, 12, and X. Correlation of the expression of human gene loci with the h...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1975-09-01 00:00:00
abstract::Bulimia nervosa (BN) is strongly familial, and additive genetic effects appear to contribute substantially to the observed familiality. In turn, behavioral components of BN, such as self-induced vomiting, are reliably measured and heritable. To identify regions of the genome harboring genetic variants conferring susce...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/345801
更新日期:2003-01-01 00:00:00
abstract::The definition of haplotype blocks of single-nucleotide polymorphisms (SNPs) has been proposed so that the haplotypes can be used as markers in association studies and to efficiently describe human genetic variation. The International Haplotype Map (HapMap) project to construct a comprehensive catalog of haplotypic va...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/498175
更新日期:2005-12-01 00:00:00
abstract::One widely used measure of genetic similarity for pairs of relatives is gene identity-by-descent (IBD) sharing. Genes that are copies of a single gene in a common ancestor of the individuals who now carry them are said to be IBD. One obvious extension of the IBD concept is IBD gene(s) shared by more than two individua...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::Autosomal dominant progressive external ophthalmoplegia (adPEO) is a disorder characterized by ptosis, progressive weakness of the external eye muscles, and general muscle weakness. The patients have multiple deletions of mtDNA on Southern blots or in PCR analysis of muscle DNA and a mild deficiency of one or more res...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-04-01 00:00:00
abstract::In order to evaluate the role of inherited BRCA2 mutations in American families--particularly the appearance in America of European founder mutations--the BRCA2 coding sequence, 5' UTR, and 3' UTR were screened in 22 Caucasian American kindreds with four or more cases of breast or ovarian cancer. Six mutations were fo...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1997-05-01 00:00:00
abstract::Heteroplasmy, the existence of multiple mtDNA types within an individual, has been previously detected by using mostly indirect methods and focusing largely on just the hypervariable segments of the control region. Next-generation sequencing technologies should enable studies of heteroplasmy across the entire mtDNA ge...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2010.07.014
更新日期:2010-08-13 00:00:00
abstract::Diabetes mellitus and neurodegeneration are common diseases for which shared genetic factors are still only partly known. Here, we show that loss of the BiP (immunoglobulin heavy-chain binding protein) co-chaperone DNAJC3 leads to diabetes mellitus and widespread neurodegeneration. We investigated three siblings with ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2014.10.013
更新日期:2014-12-04 00:00:00
abstract::Hereditary fructose intolerance (HFI) is a potentially fatal autosomal recessive disease of carbohydrate metabolism. HFI patients exhibit a deficiency of fructose 1-phosphate aldolase (aldolase B), the isozyme expressed in tissues that metabolize fructose. The eight protein-coding exons, including splicing signals, of...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-11-01 00:00:00
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
更新日期:2007-07-01 00:00:00