Abstract:
:Progressive X-linked cone-rod dystrophy (COD1) is a retinal disease affecting primarily the cone photoreceptors. The COD1 locus originally was localized, by the study of three independent families, to a region between Xp11.3 and Xp21.1, encompassing the retinitis pigmentosa (RP) 3 locus. We have refined the COD1 locus to a limited region of Xp11.4, using two families reported elsewhere and a new extended family. Genotype analysis was performed by use of eight microsatellite markers (tel-M6CA, DXS1068, DXS1058, DXS993, DXS228, DXS1201, DXS1003, and DXS1055-cent), spanning a distance of 20 cM. Nine-point linkage analysis, by use of the VITESSE program for X-linked disorders, established a maximum LOD score (17.5) between markers DXS1058 and DXS993, spanning 4.0 cM. Two additional markers, DXS977 and DXS556, which map between DXS1058 and DXS993, were used to further narrow the critical region. The RP3 gene, RPGR, was excluded on the basis of two obligate recombinants, observed in two independent families. In a third family, linkage analysis did not exclude the RPGR locus. The entire coding region of the RPGR gene from two affected males from family 2 was sequenced and was found to be normal. Haplotype analysis of two family branches, containing three obligate recombinants, two affected and one unaffected, defined the COD1 locus as distal to DXS993 and proximal to DXS556, a distance of approximately 1.0 Mb. This study excludes COD1 as an allelic variant of RP3 and establishes a novel locus that is sufficiently defined for positional cloning.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Seymour AB,Dash-Modi A,O'Connell JR,Shaffer-Gordon M,Mah TS,Stefko ST,Nagaraja R,Brown J,Kimura AE,Ferrell RE,Gorin MBdoi
10.1086/301667subject
Has Abstractpub_date
1998-01-01 00:00:00pages
122-9issue
1eissn
0002-9297issn
1537-6605pii
S0002-9297(07)60129-3journal_volume
62pub_type
杂志文章abstract::The effects of reproductive compensation on an X-linked recessive lethal are examined. Complete compensation without regard to the sex of the offspring increases the incidence of female carriers by a factor of 1.5, and of affected males by 1.33. However, if families reproduce until they have a healthy male offspring, ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1980-07-01 00:00:00
abstract::X chromosome- and Y chromosome-specific DNA probes were used to study different aspects of the genesis of sex-chromosome monosomy. Using X-linked RFLPs, we studied the parental origin of the single X chromosome in 35 spontaneously aborted and five live-born 45,X conceptions. We determined the origin in 35 cases; 28 ha...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1988-04-01 00:00:00
abstract::The ascertainment problem arises when families are sampled by a nonrandom process and some assumption about this sampling process must be made in order to estimate genetic parameters. Under classical ascertainment assumptions, estimation of genetic parameters cannot be separated from estimation of the parameters of th...
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::Nine markers from the pericentromeric region of chromosome 17 were typed in 16 British and five South African families with neurofibromatosis type 1 (NF1). The markers--p17H8, pHHH202, and EW204--were linked to NF1 at recombination fractions less than 1%. No evidence of locus heterogeneity was detected. Inspection of ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1989-01-01 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::The May-Hegglin anomaly (MHA) is an autosomal dominant platelet disorder of unknown etiology. It is characterized by thrombocytopenia, giant platelets, and leukocyte inclusion bodies, and affected heterozygotes are predisposed to bleeding episodes. The MHA gene has recently been localized, by means of linkage analysis...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302873
更新日期:2000-04-01 00:00:00
abstract::Pelizaeus-Merzbacher disease (PMD) is an X-linked, dysmyelinating disorder of the CNS. Duplications of the proteolipid protein (PLP) gene have been found in a proportion of patients, suggesting that, in addition to coding-region or splice-site mutations, overdosage of the gene can cause PMD. We show that the duplicati...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301933
更新日期:1998-07-01 00:00:00
abstract::The genomic sequences recognized by the anonymous probe 767 (DXS115) are localized to two sites within Xq28. One site lies within intron 22 of the factor VIII gene (FBC). Physical mapping suggests that the second site lies within 1.2 megabases of the F8C gene. The RFLPs detected by 767 are located within the second si...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract::Genome-wide association studies (GWASs) have been successful in detecting variants correlated with phenotypes of clinical interest. However, the power to detect these variants depends on the number of individuals whose phenotypes are collected, and for phenotypes that are difficult to collect, the sample size might be...
journal_title:American journal of human genetics
pub_type: 杂志文章,meta分析
doi:10.1016/j.ajhg.2016.04.013
更新日期:2016-07-07 00:00:00
abstract::Bardet-Biedl syndrome (BBS) is a genetically heterogeneous, pleiotropic human disorder characterized by obesity, retinopathy, polydactyly, renal and cardiac malformations, learning disabilities, and hypogenitalism. Eight BBS loci have been mapped, and seven genes have been identified. BBS3 was previously mapped to chr...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/423903
更新日期:2004-09-01 00:00:00
abstract::Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syn...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::The authors had previously mapped a new locus-DFNA17, for nonsyndromic hereditary hearing impairment-to chromosome 22q12.2-q13. 3. DFNA17 spans a 17- to 23-cM region, and MYH9, a nonmuscle-myosin heavy-chain gene, is located within the linked region. Because of the importance of myosins in hearing, MYH9 was tested as ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/S0002-9297(07)62942-5
更新日期:2000-11-01 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::Treacher Collins syndrome (TCS) is an autosomal dominant disorder of craniofacial development, the features of which include conductive hearing loss and cleft palate. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified. In the current investigation, 25 previously undescribed mut...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract::The fragile X syndrome is due to the new class of dynamic mutations. It is associated with an expansion of a trinucleotide repeat (CGG) in exon 1 of the fragile X mental retardation gene 1 gene (FMR1). Here we present a fragile X family with an unique female patient who was rendered hemizygous for the FRAXA locus due ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/514872
更新日期:1997-10-01 00:00:00
abstract::A reproducible and convenient method for assaying glucocerebrosidase activity using the natural substrates has been developed. From the insoluble pellet fraction of cultured skin fibroblast homogenates, released glucose was measured enzymically using hexokinase coupled with the glucose-6-phosphate dehydrogenase (G6PD)...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1980-09-01 00:00:00
abstract::Idiopathic scoliosis (IS) is the most common spinal deformity in children, and its etiology is unknown. To refine the search for genes underlying IS susceptibility, we ascertained a new cohort of 52 families and conducted a follow-up study of genomewide scans that produced evidence of linkage and association with 8q12...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/513571
更新日期:2007-05-01 00:00:00
abstract::The identification of genetic variants implicated in human developmental disorders has been revolutionized by second-generation sequencing combined with international pooling of cases. Here, we describe seven individuals who have diverse yet overlapping developmental anomalies, and who all have de novo missense FBXW11...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.07.005
更新日期:2019-09-05 00:00:00
abstract::Stickler syndrome is a dominantly inherited disorder characterized by arthropathy, midline clefting, hearing loss, midfacial hypoplasia, myopia, and retinal detachment. These features are highly variable both between and within families. Mutations causing the disorder have been found in the COL2A1 and COL11A1 genes. P...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/S0002-9297(07)62938-3
更新日期:2000-11-01 00:00:00
abstract::Hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, is caused by mutations in genes involved in the transforming growth factor beta (TGF-β) signaling pathway (ENG, ACVRL1, and SMAD4). Yet, approximately 15% of individuals with clinical features of HHT do not have mutations in thes...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.07.004
更新日期:2013-09-05 00:00:00
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:
更新日期:1991-02-01 00:00:00
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::Meckel syndrome (MKS) is a lethal malformation disorder characterized classically by encephalocele, polycystic kidneys, and polydactyly. MKS is also one of the major contributors to syndromic neural tube defects (NTDs). Recent findings have shown primary cilia dysfunction in the molecular background of MKS, indicating...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.05.004
更新日期:2008-06-01 00:00:00
abstract::Integration of detailed phenotype information with genetic data is well established to facilitate accurate diagnosis of hereditary disorders. As a rich source of phenotype information, electronic health records (EHRs) promise to empower diagnostic variant interpretation. However, how to accurately and efficiently extr...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.05.010
更新日期:2018-07-05 00:00:00
abstract::Limb-girdle muscular dystrophies (LGMDs) are a group of neuromuscular diseases presenting great clinical heterogeneity. Mutations in CANP3, the gene encoding muscle-specific calpain, were used to identify this gene as the genetic site responsible for autosomal recessive LGMD type 2A (LGMD2A; MIM 253600). Analyses of t...
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::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::Exome sequencing has markedly enhanced the discovery of genes implicated in Mendelian disorders, particularly for individuals in whom a known clinical entity could not be assigned. This has led to the recognition that phenotypic heterogeneity resulting from allelic mutations occurs more commonly than previously apprec...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2017.12.015
更新日期:2018-02-01 00:00:00
abstract::The sibship disequilibrium test (SDT) is designed to detect both linkage in the presence of association and association in the presence of linkage (linkage disequilibrium). The test does not require parental data but requires discordant sibships with at least one affected and one unaffected sibling. The SDT has many d...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302137
更新日期:1998-12-01 00:00:00
abstract::Steroid-resistant nephrotic syndrome (SRNS) is characterized by high-range proteinuria and most often focal and segmental glomerulosclerosis (FSGS). Identification of mutations in genes causing SRNS has improved our understanding of disease mechanisms and highlighted defects in the podocyte, a highly specialized glome...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.12.016
更新日期:2019-02-07 00:00:00
abstract::Export of mRNA from the cell nucleus to the cytoplasm is essential for protein synthesis, a process vital to all living eukaryotic cells. mRNA export is highly conserved and ubiquitous. Mutations affecting mRNA and mRNA processing or export factors, which cause aberrant retention of mRNAs in the nucleus, are thus emer...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2015.05.021
更新日期:2015-08-06 00:00:00