Abstract：
:Eighty unrelated individuals with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) were found to have deletions in the major deletion-rich region of the DMD locus. This region includes the last five exons detected by cDNA5b-7, all exons detected by cDNA8, and the first two exons detected by cDNA9. These 80 individuals account for approximately 75% of 109 deletions of the gene, detected among 181 patients analyzed with the entire dystrophin cDNA. Endpoints for many of these deletions were further characterized using two genomic probes, p20 (DXS269; Wapenaar et al.) and GMGX11 (DXS239; present paper). Clinical findings are presented for all 80 patients allowing a correlation of phenotypic severity with the genotype. Thirty-eight independent patients were old enough to be classified as DMD, BMD, or intermediate phenotype and had deletions of exons with sequenced intron/exon boundaries. Of these, eight BMD patients and one intermediate patient had gene deletions predicted to leave the reading frame intact, while 21 DMD patients, 7 intermediate patients, and 1 BMD patient had gene deletions predicted to disrupt the reading frame. Thus, with two exceptions, frameshift deletions of the gene resulted in more severe phenotype than did in-frame deletions. This is in agreement with recent findings by Baumbach et al. and Koenig et al. but is in contrast to findings, by Malhotra et al., at the 5' end of the gene.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Gillard EF,Chamberlain JS,Murphy EG,Duff CL,Smith B,Burghes AH,Thompson MW,Sutherland J,Oss I,Bodrug SEsubject
Has Abstract,Author List Incompletepub_date
1989-10-01 00:00:00pages
507-20issue
4eissn
0002-9297issn
1537-6605journal_volume
45pub_type
杂志文章abstract：:Genes comprising the major histocompatibility complex (MHC) play a central role in governing the immune response of vertebrates. A great deal of information has been revealed on the molecular biology and physiology of these loci, but three features-the high polymorphism, tight linkage among the loci, and the nonrandom...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
abstract：:Epileptic encephalopathy (EE) refers to a clinically and genetically heterogeneous group of severe disorders characterized by seizures, abnormal interictal electro-encephalogram, psychomotor delay, and/or cognitive deterioration. We ascertained two multiplex families (including one consanguineous family) consistent wi...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2014.06.006
更新日期：2014-07-03 00:00:00
abstract：:The introduction of stochastic methods in pedigree analysis has enabled geneticists to tackle computations intractable by standard deterministic methods. Until now these stochastic techniques have worked by running a Markov chain on the set of genetic descent states of a pedigree. Each descent state specifies the path...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:Ninety extended families having one or more individuals affected with nonsyndromic cleft lip (CL) with or without cleft palate (CL/P) were ascertained in rural West Bengal, India. These families included 138 affected people, 64% of whom had CL alone and 66% of whom were male. Multiple-affected-member ("multiplex") ped...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：:Myoclonus-dystonia (M-D) is an autosomal dominant disorder characterized by myoclonic and dystonic muscle contractions that are often responsive to alcohol. The dopamine D2 receptor gene (DRD2) on chromosome 11q has been implicated in one family with this syndrome, and linkage to a 28-cM region on 7q has been reported...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：2000-11-01 00:00:00
abstract：:Attention-deficit/hyperactivity disorder (ADHD [MIM 143465]) is a common, highly heritable neurobehavioral disorder of childhood onset, characterized by hyperactivity, impulsivity, and/or inattention. As part of an ongoing study of the genetic etiology of ADHD, we have performed a genomewide linkage scan in 204 nuclea...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/375139
更新日期：2003-05-01 00:00:00
abstract：:Two new morphs (F and G) detected by the centromeric alpha satellite probe p alpha 10RP8 and D10Z1 in HinfI digests are linked to the PstI polymorphisms of D10Z1, confirming their chromosome 10 location. The F and G morphs were in strong linkage disequilibrium with each other but were in weak linkage disequilibrium wi...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-12-01 00:00:00
abstract：:Inhibition of replicative DNA synthesis following gamma-irradiation is observed in eukaryotic cells but is defective in cells derived from patients with the cancer-prone inherited disorder ataxia-telangiectasia (A-T) and in A-T-like Chinese hamster cell mutants. Chinese hamster cells show a less pronounced inhibition ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-11-01 00:00:00
abstract：:Loss-of-heterozygosity (LOH) studies have implicated one or more chromosome 11 tumor-suppressor gene(s) in the development of cutaneous melanoma as well as a variety of other forms of human cancer. In the present study, we have identified multiple independent critical regions on this chromosome by use of homozygosity ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302999
更新日期：2000-08-01 00:00:00
abstract：:We have identified a new mutation in mtDNA, involving tRNALeu(CUN) in a patient manifesting an isolated skeletal myopathy. This heteroplasmic A-->G transition at position 12320 affects the T psi C loop at a conserved site and was not found in 120 controls. Analysis of cultured fibroblasts, white blood cells/platelets,...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1997-02-01 00:00:00
abstract：:We consider sequential sampling of pedigrees for genetic analysis. Cannings and Thompson (1977) gave simple, general guidelines for valid sequential sampling schemes. We show that their formulation of the likelihood contains an error, which is, however, easily corrected so as to maintain the validity of the sequential...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-08-01 00:00:00
abstract：:Recent studies suggest that hereditary prostate cancer is a complex disease involving multiple susceptibility genes and variable phenotypic expression. While conducting a genomewide search on 162 North American families with > or =3 members affected with prostate cancer (PRCA), we found evidence for linkage to chromos...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302994
更新日期：2000-07-01 00:00:00
abstract：:Meta-analysis of genome-wide association studies (GWASs) has led to the discoveries of many common variants associated with complex human diseases. There is a growing recognition that identifying "causal" rare variants also requires large-scale meta-analysis. The fact that association tests with rare variants are perf...
journal_title：American journal of human genetics
pub_type： 杂志文章,meta分析
doi：10.1016/j.ajhg.2013.06.011
更新日期：2013-08-08 00:00:00
abstract：:Interleukin-12 (IL12) is a cytokine that is secreted by activated phagocytes and dendritic cells and that induces interferon-gamma production by natural-killer and T lymphocytes. It consists of two subunits, p35 and p40, which are encoded by IL12A and IL12B, respectively. The first reported patient with a genetic cyto...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/338625
更新日期：2002-02-01 00:00:00
abstract：:We report here an evaluation of 55 pregnancies at risk for a sickle hemoglobinopathy prenatally diagnosed by restriction-endonuclease analysis, with the endonucleases MstII and HpaI, of amniocyte DNA. The diagnosis was completed in all cases. Eleven fetuses were predicted to be affected, of which six were terminated. ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1987-06-01 00:00:00
abstract：:The first 14 exons of the APC gene have been screened by the denaturation gradient gel electrophoresis method in 160 unrelated patients with familial adenomatous polyposis coli (APC) syndrome. Four polymorphic variants corresponding to silent mutations not associated with the disease phenotype were observed. Mutations...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-02-01 00:00:00
abstract：:D1S1, a human anonymous DNA clone originally called lambda Ch4A-H3 or lambda H3, was mapped by two other laboratories to human chromosome 1p36 by in situ hybridization but its localization was not confirmed using a different mapping method. We used a panel of human-hamster somatic cell hybrids to show that there are c...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-04-01 00:00:00
abstract：:Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2008.08.002
更新日期：2008-09-01 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：:Chromosomal aneuploidy is usually identified by cytogenetic methods. However, for some purposes it would be desirable to have an easier method of recognizing specific trisomies or monosomies. We have devised such an assay. It involves the simultaneous hybridization of two chromosome-specific DNA probes labeled with di...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:We examined the burden of large, rare, copy-number variants (CNVs) in 192 individuals with renal hypodysplasia (RHD) and replicated findings in 330 RHD cases from two independent cohorts. CNV distribution was significantly skewed toward larger gene-disrupting events in RHD cases compared to 4,733 ethnicity-matched con...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.10.007
更新日期：2012-12-07 00:00:00
abstract：:Our previous studies have revealed a higher frequency of nonpolymorphic electrophoretic variants in blood samples from Amerindians than in similar samples from Caucasians and Japanese. Our present study finds, by contrast, that the frequency of deficiency variants of 11 erythrocyte enzymes, sampled in nine Amerindian ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
abstract：:Early B cell factor 3 (EBF3) is an atypical transcription factor that is thought to influence the laminar formation of the cerebral cortex. Here, we report that de novo mutations in EBF3 cause a complex neurodevelopmental syndrome. The mutations were identified in two large-scale sequencing projects: the UK Decipherin...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2016.11.020
更新日期：2017-01-05 00:00:00
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：
更新日期：1996-08-01 00:00:00
abstract：:We tested 519 chromosome 3-specific cosmids for the presence of rare restriction-endonuclease sites in a search for cosmids containing HTF islands. We have identified 49 cosmids (9% of those tested) that contain multiple rare restriction-endonuclease sites. The cosmids were digested with several common cutting restric...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-09-01 00:00:00
abstract：:Huntington disease (HD) is a dominantly inherited neurodegenerative disorder characterized by dysregulation of various genes. Recently, microRNAs (miRNAs) have been reported to be involved in this dysregulation, suggesting that manipulation of appropriate miRNA regulation may have a therapeutic benefit. Here, we repor...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.05.025
更新日期：2013-08-08 00:00:00
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
更新日期：2008-01-01 00:00:00
abstract：:Hypotrichosis simplex (HS) comprises a group of hereditary isolated alopecias that are characterized by a diffuse and progressive loss of hair starting in childhood and shows a wide phenotypic variability. We mapped an autosomal-dominant form of HS to chromosome 1q31.3-1q41 in a Spanish family. By direct sequencing, w...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.10.022
更新日期：2013-01-10 00:00:00
abstract：:Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low-density-lipoprotein (LDL) receptor. Here we characterize an LDL-receptor founder mutation that is associated with a distinct LDL-receptor haplotype and is responsible for FH in 35% of 71 Jewish-Ashkenazi FH families in I...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
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
更新日期：2011-01-07 00:00:00
