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 score of 3.1 was obtained at IFNGR1, the gene that encodes chain 1 of the interferon-gamma (IFN-gamma) receptor. Sequencing of IFNGR1 revealed -56C-->T, H318P, and L450P variants, which were found to be associated with high antibody concentrations. The inclusion of these in the linkage analysis raised the LOD score to 4.2. The variants were more prevalent in Africans than in whites. Our findings indicate that IFN-gamma signaling plays an essential role in human H. pylori infection, and they contribute to an explanation of the observations of high prevalences and relatively low pathogenicity of H. pylori in Africa. Moreover, they provide further support for the value of genomewide linkage studies in the analysis of susceptibility to infection and other complex genetic traits.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Thye T,Burchard GD,Nilius M,Müller-Myhsok B,Horstmann RDdoi
10.1086/367714subject
Has Abstractpub_date
2003-02-01 00:00:00pages
448-53issue
2eissn
0002-9297issn
1537-6605pii
S0002-9297(07)60553-9journal_volume
72pub_type
杂志文章abstract::Sixteen tyrosinemic patients were evaluated in our institution for a possible liver transplantation. All patients showed biochemical and/or radiological evidence of liver dysfunction. Renal involvement was found to be more abnormal than expected. Seven patients have been transplanted, with two patients receiving a com...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1990-08-01 00:00:00
abstract::Cerebello-oculo-renal syndromes (CORSs) and Joubert syndrome (JS) are clinically and genetically heterogeneous autosomal recessive syndromes that share a complex neuroradiological malformation resembling a molar tooth on brain axial images, a condition referred to as "molar tooth on imaging" (MTI) or the "molar tooth ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/378241
更新日期:2003-09-01 00:00:00
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 CO...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-07-01 00:00:00
abstract::Two pregnancies at risk for glutaric acidemia were monitored. In one, in which the fetus was not affected, glutaric acid was not detected in the amniotic fluid at amniocentesis (15 weeks) and the glutaryl-CoA dehydrogenase activity of cultured amniotic cells was normal. In the other, a marked elevation of glutaric aci...
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::Focal cortical dysplasia (FCD) is a major cause of the sporadic form of intractable focal epilepsies that require surgical treatment. It has recently been reported that brain somatic mutations in MTOR account for 15%-25% of FCD type II (FCDII), characterized by cortical dyslamination and dysmorphic neurons. However, t...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2017.01.030
更新日期:2017-03-02 00:00:00
abstract::Complementary genetic and demographic analyses estimate the total proportion of European-American admixture in the Gila River Indian Community and trace its mode of entry. Among the 9,616 residents in the sample, 2,015 persons claim only partial Native American heritage. A procedure employing 23 alleles or haplotypes ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-07-01 00:00:00
abstract::Genetic mutations responsible for oblique facial clefts (ObFC), a unique class of facial malformations, are largely unknown. We show that loss-of-function mutations in SPECC1L are pathogenic for this human developmental disorder and that SPECC1L is a critical organizer of vertebrate facial morphogenesis. During murine...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2011.05.023
更新日期:2011-07-15 00:00:00
abstract::Richieri-Costa-Pereira syndrome is an autosomal-recessive acrofacial dysostosis characterized by mandibular median cleft associated with other craniofacial anomalies and severe limb defects. Learning and language disabilities are also prevalent. We mapped the mutated gene to a 122 kb region at 17q25.3 through identity...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.11.020
更新日期:2014-01-02 00:00:00
abstract::Mutations in the MCOLN1 gene cause mucolipidosis type IV (MLIV), a severely debilitating, autosomal recessive, lysosomal storage disorder. Approximately 80% of patients with MLIV are of Ashkenazi Jewish (AJ) descent, and two mutations, IVS3-2A-->G and 511del6434, account for >95% of the mutant alleles in this populati...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/339519
更新日期:2002-04-01 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::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::The original test for the analysis of the CCG expansion at the FRAXE locus involves Southern blot analysis of HindIII digests. We show that, by using a different probe, the FRAXE mutation can be detected easily on the same EcoRI or EagI+EcoRI blots as are used for detection of FRAXA. Unexpectedly, we found that both t...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::Joubert syndrome and related disorders (JSRD) are primarily autosomal-recessive conditions characterized by hypotonia, ataxia, abnormal eye movements, and intellectual disability with a distinctive mid-hindbrain malformation. Variable features include retinal dystrophy, cystic kidney disease, and liver fibrosis. JSRD ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.10.002
更新日期:2008-11-01 00:00:00
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:
更新日期:1994-06-01 00:00:00
abstract::Neurodegeneration with brain iron accumulation (NBIA) is a group of genetic disorders characterized by abnormal iron deposition in the basal ganglia. We report that de novo mutations in WDR45, a gene located at Xp11.23 and encoding a beta-propeller scaffold protein with a putative role in autophagy, cause a distinctiv...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.10.019
更新日期:2012-12-07 00:00:00
abstract::Pedigrees used in the analysis of genetic or medical data are usually ascertained from sources subject to a variety of errors including misidentification of individuals, faults in historical documents or record linkage, nonpaternity, and unidentified adoption. Genetic markers can be used to verify putative family and ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
abstract::We analyzed mutations and defined the chromosomal haplotype in 127 patients and Mediterranean descent who were affected by Wilson disease (WD), 39 Sardinians, 49 Italians, 33 Turks, and 6 Albanians. Haplotypes were derived by use of the microsatellite markers D13S301, D13S296, D13S297, and D13S298, which are linked to...
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::Carpenter syndrome is an autosomal-recessive multiple-congenital-malformation disorder characterized by multisuture craniosynostosis and polysyndactyly of the hands and feet; many other clinical features occur, and the most frequent include obesity, umbilical hernia, cryptorchidism, and congenital heart disease. Mutat...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.08.027
更新日期:2012-11-02 00:00:00
abstract::The results of an empirical nucleotide-sequencing approach indicate that the evolution of the human mitochondrial noncoding D-loop is both more rapid and more complex than is revealed by standard phylogenetic approaches. The nucleotide sequence of the D-loop region of the mitochondrial genome was determined for 45 mem...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::In recent years, many genomewide screens have been performed, to identify novel loci predisposing to various complex diseases. Often, only a portion of the collected clinical data from the study subjects is used in the actual analysis of the trait, and much of the phenotypic data is ignored. With proper consent, these...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/321286
更新日期:2001-07-01 00:00:00
abstract::We have evaluated eight patients with pigmentary anomalies reminiscent of incontinentia pigmenti or hypomelanosis of Ito. All demonstrated abnormal lymphocyte karyotypes with chromosomal mosaicism in lymphocytes and/or skin fibroblasts. In seven the skin was darkly pigmented, and in all of these seven cases the abnorm...
journal_title:American journal of human genetics
pub_type: 杂志文章,评审
doi:
更新日期:1989-08-01 00:00:00
abstract::Gilles de la Tourette syndrome (GTS) is characterized by multiple motor and phonic tics and high comorbidity rates with other neurobehavioral disorders. It is hypothesized that frontal-subcortical pathways and a complex genetic background are involved in the etiopathogenesis of the disorder. The genetic basis of GTS r...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/424389
更新日期:2004-10-01 00:00:00
abstract::Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. We report the first major genomewide screen of multiplex families with RA gathered in the United States. The North American Rheumatoid Arthritis Consortium, using well-defined clinical criteria, has collected 257 familie...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/319518
更新日期:2001-04-01 00:00:00
abstract::We have previously shown that intracellular trafficking and extracellular assembly of tropoelastin into elastic fibers is facilitated by the 67-kD elastin-binding protein identical to an enzymatically inactive, alternatively spliced variant of beta-galactosidase (S-Gal). In the present study, we investigated elastic-f...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302968
更新日期:2000-07-01 00:00:00
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
更新日期:2004-11-01 00:00:00
abstract::The Hawaii Family Study of Cognition provided an opportunity to investigate the frequency and implications of non-agreement, or mismatches, between observed and expected genetic marker phenotypes of husbands, wives, and children. Mismatch data from 68 families in which one or both spouses were known not to be a biolog...
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::Argininosuccinate lyase (AS lyase) deficiency is an inborn error of the urea cycle with extensive clinical and genetic heterogeneity. We investigated the biochemical basis of the enzyme defect and the genetic heterogeneity in this disorder using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1986-07-01 00:00:00
abstract::A non-Jewish family is presented in which the genes for Tay-Sachs disease and Sandhoff disease are segregating. Individuals heterozygous for both alleles have low serum and white cell total hexosaminidase levels together with a proportion of heat-labile hexosaminidase A (HEX A) which falls in the normal range. The ind...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1980-11-01 00:00:00
abstract::Attention-deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed behavioral disorder in childhood and likely represents an extreme of normal behavior. ADHD significantly impacts learning in school-age children and leads to impaired functioning throughout the life span. There is strong evidence for a gene...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/342732
更新日期:2002-10-01 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