Abstract:
:It has been proposed that gluten sensitive enteropathy (GSE) results from the interaction of two loci: one locus linked to HLA and associated with dominant inheritance, and the other, a non-HLA-linked GSE-associated B-cell alloantigen, exhibiting recessive inheritance. We have shown in previous analyses that a two-locus, dominant-recessive model is less compatible with the existing population prevalence and observed familial segregation data than is a recessive-recessive two-locus model. Here we present additional analyses of reported population and familial HLA data that support the recessive mode of inheritance for the HLA-linked disease locus. Reported data from HLA typing of affected sib pairs, the association of GSE with DR3 and DR7 in different populations, and the proportions of different HLA phenotypes and genotypes were compared with expected data derived by three different methods. The HLA data analyses consistently reject a dominant mode of inheritance for the presumed HLA-linked disease allele but do not reject a recessive model. The affected sib-pair data also support a recessive model. These analyses are consistent with our previous prediction that the HLA-"linked" disease allele in GSE is recessive inherited.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Greenberg DA,Hodge SE,Rotter JIsubject
Has Abstractpub_date
1982-03-01 00:00:00pages
263-77issue
2eissn
0002-9297issn
1537-6605journal_volume
34pub_type
杂志文章abstract::Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to e...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.11.002
更新日期:2019-01-03 00:00:00
abstract::Suppose that many polymorphic sites have been identified and genotyped in a region showing strong linkage with a trait. A key question of interest is which site (or combination of sites) in the region influences susceptibility to the trait. We have developed a novel statistical approach to this problem, in the context...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/338660
更新日期:2002-02-01 00:00:00
abstract::Nondisjunction in trisomy 21 has traditionally been studied by cytogenetic heteromorphisms. Those studies assumed no crossing-over on the short arm of chromosome 21. Recently, increased accuracy of detection of the origin of nondisjunction has been demonstrated by DNA polymorphism analysis. We describe a comparative s...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-09-01 00:00:00
abstract::DNA from over 2,000 Ashkenazi Jewish subjects has been examined for the four most common Jewish Gaucher disease mutations, which collectively account for about 96% of the disease-producing alleles in Jewish patients. This population survey has made possible the estimation of gene frequencies for these alleles. Eighty-...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-01-01 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::Fragile X premutations are considered to be a risk factor for premature ovarian failure (POF), which is usually defined as menopause at age <40 years. Since premutations may be inherited from either the mother or the father, we evaluated the influence of the inheritance pattern on the duration of reproductive life in ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302774
更新日期:2000-02-01 00:00:00
abstract::Genetic mapping of complex diseases to date depends on variations inside or close to the genes that perturb their activities. A strong body of evidence suggests that changes in gene expression play a key role in complex diseases and that numerous loci perturb gene expression in trans. The information in trans variants...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.03.022
更新日期:2013-05-02 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::Neurofibromatosis 2 (NF2) is a genetic disorder characterized by the development of multiple nervous-system tumors in young adulthood. The NF2 gene has recently been isolated and found to encode a new member of the protein 4.1 family of cytoskeletal associated proteins, which we have named merlin. To define the molecu...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-08-01 00:00:00
abstract::The practicality and moral value of community review of human genetic research has become a focus of debate. Examples from two Native American communities are used to address four aspects of that debate: (1) the value of community review in larger, geographically dispersed populations; (2) the identification of cultur...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302415
更新日期:1999-06-01 00:00:00
abstract::A previously unrecognized autosomal dominant syndrome affecting oral, nasal, vaginal, urethral, anal, bladder, and conjunctival mucosa with cataracts, follicular keratosis, nonscarring alopecia, and terminal lung disease is described in a four-generation kindred of German extraction. Severe photophobia, tearing, and n...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1979-07-01 00:00:00
abstract::Lissencephaly comprises a spectrum of malformations of cortical development. This spectrum includes agyria, pachygyria, and subcortical band heterotopia; each represents anatomical malformations of brain cortical development caused by neuronal migration defects. The molecular etiologies of neuronal migration anomalies...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.09.017
更新日期:2019-11-07 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::The association between normal alleles at the CTG repeat and two nearby polymorphisms in the myotonin protein kinase gene, the Alu insertion/deletion polymorphism and the myotonic dystrophy kinase (DMK)(G/T) intron 9/HinfI polymorphism, has been analyzed in South African Negroids, a population in which myotonic dystro...
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::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::Lumbar-disc herniation (LDH), one of the most common musculoskeletal diseases, has strong genetic determinants. Recently, several genes that encode extracellular matrix (ECM) proteins in the intervertebral disc have been reported to associate with LDH. Thrombospondins (THBSs) 1 and 2 are good candidates for the LDH su...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.03.013
更新日期:2008-05-01 00:00:00
abstract::Multiprotein complexes referred to as outer dynein arms (ODAs) develop the main mechanical force to generate the ciliary and flagellar beat. ODA defects are the most common cause of primary ciliary dyskinesia (PCD), a congenital disorder of ciliary beating, characterized by recurrent infections of the upper and lower ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.06.014
更新日期:2016-08-04 00:00:00
abstract::One approach frequently used for identifying genetic factors involved in the process of a complex disease is the comparison of patients and controls for a number of genetic markers near a candidate gene. The analysis of such association studies raises some specific problems because of the fact that genotypic and not g...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-05-01 00:00:00
abstract::In the present work, we demonstrate the possibility of using human blood platelets as mitochondrial donors for the repopulation of mtDNA-less (rho 0) cells. The noninvasive nature of platelet isolation, combined with the prolonged viability of platelet mitochondria and the simplicity and efficiency of the mitochondria...
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::Linkage of Alzheimer disease (AD) to DNA markers on chromosomes 14, 19, and 21 was studied in 10 families in which the disease was apparently inherited as an autosomal dominant trait. Families were derived from a Dutch population-based epidemiologic study of early-onset AD. Although in all probands the onset of AD was...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-10-01 00:00:00
abstract::There is an inverse relationship between serum bilirubin concentrations and risk of coronary artery disease. The strength of the association is similar to that of smoking, systolic blood pressure, and HDL cholesterol. We carried out a genomewide scan in a Framingham Heart Study. Our study sample consisted of 330 famil...
journal_title:American journal of human genetics
pub_type: 杂志文章,多中心研究
doi:10.1086/373964
更新日期:2003-04-01 00:00:00
abstract::Whole-genome and exome sequence data can be cost-effectively generated for the detection of rare-variant (RV) associations in families. Causal variants that aggregate in families usually have larger effect sizes than those found in sporadic cases, so family-based designs can be a more powerful approach than population...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.12.001
更新日期:2017-02-02 00:00:00
abstract::In studying the relationship between genetic abnormalities of red blood cells and malaria endemicity in the Vanuatu archipelago in the southwestern Pacific, we have found that of 1,442 males tested, 98 (6.8%) were G6PD deficient. The prevalence of GdPD deficiency varied widely (0%-39%), both from one island to another...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-01-01 00:00:00
abstract::Germline mutations of PTEN (phosphatase and tensin homolog deleted on chromosome 10) are associated with the multihamartomatous disorder Cowden syndrome (CS). Moreover, patients with CS with germline PTEN promoter mutations have aberrant PTEN protein expression and an increased frequency of breast cancer. Here, we exa...
journal_title:American journal of human genetics
pub_type: 杂志文章,多中心研究
doi:10.1086/521051
更新日期:2007-10-01 00:00:00
abstract::The Hartnup mutation affects an amino acid transport system of intestine and kidney used by a large group of neutral charge alpha-amino acids (six essential and several nonessential). We compared developmental outcomes and medical histories of 21 Hartnup subjects, identified through newborn screening, with those of 19...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1987-05-01 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::The importance of the HLA-DR locus to multiple sclerosis (MS) susceptibility was assessed in 542 sib pairs with MS and in their families. By genotyping 1,978 individuals for HLA-DRB1 alleles, we confirmed the well-established association of MS with HLA-DRB1*15 (HLA-DRB1*1501 and HLA-DRB5*0101), by the transmission/dis...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/323480
更新日期:2001-10-01 00:00:00
abstract::Miller-Dieker syndrome (MDS), a disorder manifesting the severe brain malformation lissencephaly ("smooth brain"), is caused, in the majority of cases, by a chromosomal microdeletion of the distal short arm of chromosome 17. Using human chromosome 17-specific DNA probes, we have begun a molecular dissection of the cri...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1988-11-01 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::Whole-genome sequencing (WGS) studies are being widely conducted in order to identify rare variants associated with human diseases and disease-related traits. Classical single-marker association analyses for rare variants have limited power, and variant-set-based analyses are commonly used by researchers for analyzing...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.03.002
更新日期:2019-05-02 00:00:00