Abstract:
:Ehlers-Danlos syndrome (EDS) type IV is a dominantly inherited disorder that results from mutations in the type III collagen gene (COL3A1). We studied the structure of the COL3A1 gene of an individual with EDS type IV and that of her phenotypically normal parents. The proband was heterozygous for a 2-kb deletion in COL3A1, while her father was mosaic for the same deletion in somatic and germ cells. In fibroblasts from the father, approximately two-fifths of the COL3A1 alleles carried the deletion, but only 10% of the COL3A1 alleles in white blood cells were of the mutant species. The deletion in the mutant allele extended from intron 7 into intron 11. There was a 12-bp direct repeat in intron 7 and intron 11, the latter about 60 bp 5' to the junction. At the breakpoint there was a duplication of 10 bp from intron 11 separated by an insertion of 4 bp contained within the duplicated sequence. The father was mosaic for the deletion so that the gene rearrangement occurred during his early embryonic development prior to lineage allocation. These findings suggest that at least some of the deletions seen in human genes may occur during replication, rather than as a consequence of meiotic crossing-over, and that they thus have a risk for recurrence when observed de novo.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Milewicz DM,Witz AM,Smith AC,Manchester DK,Waldstein G,Byers PHsubject
Has Abstractpub_date
1993-07-01 00:00:00pages
62-70issue
1eissn
0002-9297issn
1537-6605journal_volume
53pub_type
杂志文章abstract::We have previously shown that rheumatoid arthritis (RA) risk alleles overlap between different ethnic groups. Here, we utilize a multiethnic approach to show that we can effectively discover RA risk alleles. Thirteen putatively associated SNPs that had not yet exceeded genome-wide significance (p < 5 × 10(-8)) in our ...
journal_title:American journal of human genetics
pub_type: 杂志文章,meta分析
doi:10.1016/j.ajhg.2012.01.010
更新日期:2012-03-09 00:00:00
abstract::A family-history cancer survey was conducted on 5,486 men who underwent a radical prostatectomy, for clinically localized prostate cancer, in the Department of Urology at the Mayo Clinic during 1966-95; 4,288 men responded to the survey. Complex segregation analysis was performed to assess the genetic basis of age at ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301862
更新日期:1998-06-01 00:00:00
abstract::Colorectal cancer (CRC) heritability has been estimated to be around 30%. However, mutations in the known CRC-susceptibility genes explain CRC risk in fewer than 10% of affected individuals. Germline mutations in DNA-repair genes (DRGs) have recently been reported in CRC, but their contribution to CRC risk is largely ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.01.018
更新日期:2018-03-01 00:00:00
abstract::Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a leukodystrophy characterized by early-onset macrocephaly and delayed-onset neurological deterioration. Recessive MLC1 mutations are observed in 75% of patients with MLC. Genetic-linkage studies failed to identify another gene. We recently showed tha...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2011.02.009
更新日期:2011-04-08 00:00:00
abstract::Familial amyotrophic lateral sclerosis (FALS) affects 5%-10% of cases of amyotrophic lateral sclerosis (ALS) and is inherited as an autosomal dominant condition with incomplete penetrance. One-fifth of these cases of FALS are associated with mutations in copper/zinc-dependent superoxide dismutase (SOD1), but the gene ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/377156
更新日期:2003-08-01 00:00:00
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
更新日期:2006-04-01 00:00:00
abstract::Multiple morphological abnormalities of the sperm flagellum (MMAF) is a severe form of male infertility defined by the presence of a mosaic of anomalies, including short, bent, curled, thick, or absent flagella, resulting from a severe disorganization of the axoneme and of the peri-axonemal structures. Mutations in DN...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.07.014
更新日期:2018-09-06 00:00:00
abstract::Patients with a strong family history of breast cancer are often counseled to receive genetic screening for BRCA1 and BRCA2 mutations, the strongest known predictors of breast cancer. A major limitation of genetic testing is the number of inconclusive results due to unclassified BRCA1 and BRCA2 sequence variants. Many...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/342192
更新日期:2002-09-01 00:00:00
abstract::To improve carrier detection and prenatal diagnosis for Duchenne and Becker muscular dystrophy families, we determined allele frequencies and measures of variation for four (dC-dA)n.(dG-dT)n loci identified within a deletion-prone region of the human dystrophin gene. The loci are highly polymorphic, with predicted het...
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::Charcot-Marie-Tooth disease is characterized by length-dependent axonal degeneration with distal sensory loss and weakness, deep-tendon-reflex abnormalities, and skeletal deformities. It is caused by mutations in more than 40 genes. We investigated a four-generation family with 23 members affected by the axonal form (...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2011.07.002
更新日期:2011-08-12 00:00:00
abstract::Little is known about the genetics of nonsyndromic intellectual disability (NSID). We hypothesized that de novo mutations (DNMs) in synaptic genes explain an important fraction of sporadic NSID cases. In order to investigate this possibility, we sequenced 197 genes encoding glutamate receptors and a large subset of th...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2011.02.001
更新日期:2011-03-11 00:00:00
abstract::Curry-Jones syndrome (CJS) is a multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. Cerebellar medulloblastoma has been described in a single af...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.04.007
更新日期:2016-06-02 00:00:00
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
更新日期:2007-10-01 00:00:00
abstract::CHARGE syndrome is a well-established multiple-malformation syndrome with distinctive consensus diagnostic criteria. Characteristic associated anomalies include ocular coloboma, choanal atresia, cranial nerve defects, distinctive external and inner ear abnormalities, hearing loss, cardiovascular malformations, urogeni...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/500273
更新日期:2006-02-01 00:00:00
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
更新日期:1999-04-01 00:00:00
abstract::Supernumerary marker chromosomes (SMCs) of chromosome 15, designated "SMC(15)s," are the most common SMC in humans, accounting for as much as 60% of all those observed. We report the characterization of 46 large SMC(15)s, using both fluorescence in situ hybridization and polymerase chain reaction analysis within and d...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/379155
更新日期:2003-11-01 00:00:00
abstract::As genetic maps become denser, the effect of laboratory typing errors becomes more serious. We review a general method for detecting errors in pedigree genotyping data that is a variant of the likelihood-ratio test statistic. It pinpoints individuals and loci with relatively unlikely genotypes. Power and significance ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-01-01 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::The need for education of nurses in genetics was articulated more than 25 years ago. This article reviews the knowledge of practicing nurses about genetics as well as the content of genetics in nursing curricula. Implementation of federal legislation that mandated increased availability of genetic services and genetic...
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::Fibroblast cultures from 12 unrelated patients with classical Menkes disease were analyzed for mutations in the MNK gene, by reverse transcription-PCR (RT-PCR) and chemical cleavage mismatch detection. Mutations were observed in 10 patients, and in each case a different mutation was present. All of the mutations would...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::In spondylocostal dysostosis (SD), vertebral-segmentation defects are associated with rib anomalies. This results in short-trunk short stature, nonprogressive kyphoscoliosis, and radiological features of multiple hemivertebrae and rib fusions. SD can be familial, and both autosomal dominant and autosomal recessive (AR...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302464
更新日期:1999-07-01 00:00:00
abstract::A clinical description of an apparently classical case of type 1 GM1 gangliosidosis is presented. The patient was the first-born child of first cousins. She was diagnosed at 6 weeks and died at 6 months. beta-Galactosidase activity was deficient in cultured fibroblasts using [3H]GM1 ganglioside and [3H]ceramide-lactos...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1979-11-01 00:00:00
abstract::X-linked ichthyosis (XLI) is an inborn error of metabolism caused by steroid sulfatase (STS) deficiency. In more than 80% of XLI patients the enzyme deficiency is due to large deletions involving the entire STS gene and flanking sequences. However, some patients with the classical XLI phenotype and complete STS defici...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-03-01 00:00:00
abstract::Cranial neural crest (CNC) is a multipotent migratory cell population that gives rise to most of the craniofacial bones. An intricate network mediates CNC formation, epithelial-mesenchymal transition, migration along distinct paths, and differentiation. Errors in these processes lead to craniofacial abnormalities, inc...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2011.01.003
更新日期:2011-02-11 00:00:00
abstract::Myotonic dystrophy (DM) is a progressive neuromuscular disorder which results from elongations of an unstable (CTG)n repeat, located in the 3' untranslated region of the DM gene. A correlation has been demonstrated between the increase in the repeat number of this sequence and the severity of the disease. However, the...
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::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::An increasing number of genes involved in chromatin structure and epigenetic regulation has been implicated in a variety of developmental disorders, often including intellectual disability. By trio exome sequencing and subsequent mutational screening we now identified two de novo frameshift mutations and one de novo m...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.05.007
更新日期:2013-07-11 00:00:00
abstract::Cytokines are essential regulatory components of the immune system, and their aberrant levels have been linked to many disease states. Despite increasing evidence that cytokines operate in concert, many of the physiological interactions between cytokines, and the shared genetic architecture that underlies them, remain...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.10.001
更新日期:2019-12-05 00:00:00
abstract::Antenatal Bartter syndrome is a variant of inherited renal-tubular disorders associated with hypokalemic alkalosis. This disorder typically presents as a life-threatening condition beginning in utero, with marked fetal polyuria that leads to polyhydramnios and premature delivery. Another hallmark of this variant is a ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301872
更新日期:1998-06-01 00:00:00
abstract::The gene(s) whose expression is regulated by allergy risk variants is unknown for many loci identified through genome-wide association studies. Addressing this knowledge gap might point to new therapeutic targets for allergic disease. The aim of this study was to identify the target gene(s) and the functional variant(...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2015.06.010
更新日期:2015-08-06 00:00:00