Abstract:
:One of the central goals of human genetics is the identification of loci with alleles or genotypes that confer increased susceptibility. The availability of dense maps of single-nucleotide polymorphisms (SNPs) along with high-throughput genotyping technologies has set the stage for routine genome-wide association studies that are expected to significantly improve our ability to identify susceptibility loci. Before this promise can be realized, there are some significant challenges that need to be addressed. We address here the challenge of detecting epistasis or gene-gene interactions in genome-wide association studies. Discovering epistatic interactions in high dimensional datasets remains a challenge due to the computational complexity resulting from the analysis of all possible combinations of SNPs. One potential way to overcome the computational burden of a genome-wide epistasis analysis would be to devise a logical way to prioritize the many SNPs in a dataset so that the data may be analyzed more efficiently and yet still retain important biological information. One of the strongest demonstrations of the functional relationship between genes is protein-protein interaction. Thus, it is plausible that the expert knowledge extracted from protein interaction databases may allow for a more efficient analysis of genome-wide studies as well as facilitate the biological interpretation of the data. In this review we will discuss the challenges of detecting epistasis in genome-wide genetic studies and the means by which we propose to apply expert knowledge extracted from protein interaction databases to facilitate this process. We explore some of the fundamentals of protein interactions and the databases that are publicly available.
journal_name
Hum Genetjournal_title
Human geneticsauthors
Pattin KA,Moore JHdoi
10.1007/s00439-008-0522-8subject
Has Abstractpub_date
2008-08-01 00:00:00pages
19-29issue
1eissn
0340-6717issn
1432-1203journal_volume
124pub_type
杂志文章,评审相关文献
HUMAN GENETICS文献大全abstract::The possible influence of the fragile X mutation at Xq27 on the expression of the neighbouring gene (at Xq26) for hypoxanthine phosphoribosyl transferase (HPRT) was studied by determination of the levels of HPRT-RNA and HPRT enzyme activity in fibroblast cell cultures from 7 fragile X patients. These levels were lower...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00197177
更新日期:1991-08-01 00:00:00
abstract::Scapuloperoneal spinal muscular atrophy (SPSMA) is a neuromuscular disorder characterized by weakness in the distribution of shoulder girdle and peroneal muscles. We have previously described a large New England kindred with autosomal dominant SPSMA and have subsequently linked this family trait to 12q24.1-q24.31. In ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050435
更新日期:1997-06-01 00:00:00
abstract::Fragile sites are nonrandom, heritable sites on chromosomes that can be induced to form gaps, breaks, and rearrangements under specific conditions. There is currently no established criterion to define a common fragile site. We applied seven published criteria to our data from three groups of subjects: (1) three pairs...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00194217
更新日期:1990-10-01 00:00:00
abstract::Based upon aberrant segregation of glutamate pyruvate-transaminase (GPT) and reduced enzyme activity on electrophoresis, seven new families with a GPT null allele were identified during genetic linkage analysis for a number of different traits. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00286652
更新日期:1983-01-01 00:00:00
abstract::Congenital atrichia is a rare autosomal recessive disorder of hair development, characterized by complete loss of hair shortly after birth. Evidence of linkage to chromosome 8p12 has been established, implicating the human homolog of the mouse hairless (hr) gene as a candidate gene. We have previously identified misse...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050840
更新日期:1998-10-01 00:00:00
abstract::This paper surveys the current state of knowledge about the relationship between different national publics and biobanks, how different publics perceive biobanks, and which issues are identified as important by various stakeholders. We discuss existing studies and emerging governance strategies dealing with the bioban...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-011-1065-y
更新日期:2011-09-01 00:00:00
abstract::Polymorphism of the human c-Ha-ras-1 gene has been analysed in DNA from 168 individuals using the enzymes MspI and HpaII. In all, 35 bladder cancer patients, 28 melanoma patients, 22 Wilms' tumour patients, 24 first-degree relatives of Wilms' tumour or melanoma patients and 59 unaffected controls were studied. A total...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00278178
更新日期:1988-02-01 00:00:00
abstract::A new procedure for determining the chromosomal origin of marker chromosomes has been carried out. The origin of marker chromosomes that were unidentifiable by standard banding techniques could be verified by reverse chromosome painting. This technique includes microdissection, followed by in vitro DNA amplification a...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00201567
更新日期:1994-06-01 00:00:00
abstract::Members of three generations of a single family were examined and found to have a balanced translocation t(11;16)(q13;p11). Cytogenetic investigation and investigation of a number of gene markers is consistent with the current view that the Hp-alpha locus is situated in the proximity of band 16q22. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291626
更新日期:1978-05-16 00:00:00
abstract::Mutual correction of co-cultivated fibroblasts from patients with Hunter's and Hurler's syndrome could be inhibited by either fructose 1-phosphate or mannose 6-phosphate. In the presence of fructose 1-phosphate a 50% mixture of fibroblasts from a patient with Hunter's syndrome and a normal homozygous individual showed...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00569706
更新日期:1982-01-01 00:00:00
abstract::DNA haplotypes and frameworks (numbers in parenthesis) linked to the beta-globin gene were determined by restriction fragment analysis using eight restriction endonucleases on 86 (97) chromosomes bearing the normal beta-globin gene (HBB*A) and 108 (118) chromosomes bearing HBB*E in subjects homozygous for HBB*A or HBB...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00451464
更新日期:1988-09-01 00:00:00
abstract::The frequency of alleles for intragenic (intron 17 and intron 25) and extragenic (DXS15 and DXS52) F8C RFLPs was investigated in the Algerian population. Altogether 287 X chromosomes (97 males and 95 females) were studied. The allele frequencies found with the two intragenic F8C RFLPs were not substantially different ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00195808
更新日期:1990-04-01 00:00:00
abstract::The arbitrarily primed-PCR (AP-PCR) genomic fingerprinting method was applied to evaluate its effectiveness in detecting and characterizing amplified DNA fragments in two small-cell lung carcinoma (SCLC) cell lines, NCI-H69 and NCI-H82. Of the 2428 DNA fragments detected by AP-PCR using 62 arbitrary primers, 2 (0.08%)...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050203
更新日期:1996-09-01 00:00:00
abstract::Many studies of quantitative and disease traits in human genetics rely upon self-reported measures. Such measures are based on questionnaires or interviews and are often cheaper and more readily available than alternatives. However, the precision and potential bias cannot usually be assessed. Here we report a detailed...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-006-0240-z
更新日期:2006-11-01 00:00:00
abstract::A cosmid library was constructed from genomic DNA of a human-mouse somatic cell hybrid containing an 11q-16q translocation chromosome as the only human DNA. Cosmids with human inserts were prehybridized with total human DNA and were screened to find probes that revealed highly polymorphic loci. From one such cosmid, C...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00280499
更新日期:1986-12-01 00:00:00
abstract::A Monte Carlo simulation procedure was used to estimate the exact level of the standardized X2 test statistic (Xs2) for randomness in the FSM methodology for the identification of fragile sites from chromosomal breakage data for single individuals. A random-number generator was used to simulate 10,000 chromosomal brea...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050596
更新日期:1997-11-01 00:00:00
abstract::Multiple sclerosis (MS) is a demyelinating disorder of the central nervous system with putative autoimmune aetiology and complex genetic background. Here, we report the results of a genome screen for linkage disequilibrium (LD) by using 6000 microsatellite markers in 198 HLA-DRB1*15-positive MS patients and 198 unrela...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-002-0801-8
更新日期:2002-09-01 00:00:00
abstract::Sanfilippo syndrome type B (mucopolysaccharidosis IIIB) is a rare autosomal recessive disorder characterized by the inability to degrade heparan sulfate because of a deficiency of the lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). We performed mutation screening in a group of 20 patients, identyifing 28 mutat...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390000429
更新日期:2000-12-01 00:00:00
abstract::Deficiency in 6-pyruvoyl-tetrahydropterin synthase (PTPS) activity is the major cause of tetrahydrobiopterin (BH4)-deficient phenylketonuria. Two single base alterations of PTPS cDNA, a C-to-T transition at nucleotide 259 and a novel A-to-G transition at nucleotide 155 (according to cDNA sequence), were identified in ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050213
更新日期:1996-09-01 00:00:00
abstract::Only two genome-wide association (GWA) screens have been published for melanoma (Nat Genet 47:920-925, 2009; Nat Genet 40:838-840, 2008). Using a unique approach, we performed a genome-wide association study in 156 related melanoma cases from 34 high-risk Utah pedigrees. Genome-wide association analysis was performed ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-011-1048-z
更新日期:2012-01-01 00:00:00
abstract::Inv dup(15) is a clinically significant bisatellited derivative of chromosome 15. Five unrelated patients with this abnormality are described and compared with ten confirmed and nine suspected cases in the literature. Mental and developmental retardation, hypotonia, behavioral disturbances, seizures, abnormal dermatog...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00399391
更新日期:1979-09-01 00:00:00
abstract::Ectodermal dysplasia syndromes are genetically heterogeneous group of disorders involving one or more of the classical ectodermal appendages (hair, nail, teeth, sweat glands) in association with anomalies of other organs or systems. In the present study a novel form of ectodermal dysplasia syndrome, ectodermal dysplas...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-009-0640-y
更新日期:2009-05-01 00:00:00
abstract::Genetic factors play important roles in the development of tuberculosis (TB). SP110 is a promising candidate target for controlling TB infections. However, several studies associating SP110 single nucleotide polymorphisms (SNPs) with TB have yielded conflicting results. This may be partly resolved by studying other ge...
journal_title:Human genetics
pub_type: 杂志文章,meta分析
doi:10.1007/s00439-012-1244-5
更新日期:2013-03-01 00:00:00
abstract::During the last few years, much progress has been made in the treatment of lysosomal storage disorders. In the past, no specific therapy was available for the affected patients, and management consisted solely of supportive care and treatment of complications. Since enzyme replacement therapy has been successfully int...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/s00439-006-0280-4
更新日期:2007-03-01 00:00:00
abstract::We have studied the allele frequency distribution of the microsatellite locus DYS19 in several populations with different geographical origins worldwide. Three new alleles were found. In addition, remarkable geographic and ethnic differences were observed in the allele frequency profiles and DNA marker (gene) diversit...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF02185760
更新日期:1996-03-01 00:00:00
abstract::Acute intermittent porphyria (AIP) is a low-penetrant autosomal dominant disorder caused by mutations in the hydroxymethylbilane synthase (HMBS) gene. Direct detection of mutations is becoming the method of choice for the accurate identification of asymptomatic affected individuals within AIP families so that they can...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050995
更新日期:1999-06-01 00:00:00
abstract::Complex investigation of a spontaneous abortus with monosomy 21 was carried out. Phenotypic expression at the organism and tissue level was characterized by the pathology of the external form of the embryo and by abnormalities of the embryonic facial structures, the stomodeum, the anterior part of the primary gut, and...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00527395
更新日期:1977-09-22 00:00:00
abstract::Three patients with 45,X/46,XYnf mosaicism were investigated by Southern hybridization using both X- and Y-specific DNA probes. Our patients seem to be hemizygous for the X chromosomal loci tested. Single-copy and low-copy repeated Y chromosomal sequences assigned to the short arm, centromere, and euchromatin of the l...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00284913
更新日期:1987-06-01 00:00:00
abstract::Statistical analysis of parental age data from 225 sporadic cases of bilateral retinoblastoma, plus ten sporadic cases of chromosome deletion or translocation involving 13q14 that was identified as of paternal origin, revealed no evidence of paternal or maternal age effect. Parental exposure to ionizing radiation or c...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00208931
更新日期:1990-01-01 00:00:00
abstract::Transient neonatal diabetes mellitus (TNDM) is associated with overexpression of an imprinted locus on chromosome 6q24; this locus contains a differentially methylated region (DMR) consisting of an imprinted CpG island that normally allows expression only from the paternal allele of genes under its control. Three type...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-004-1236-1
更新日期:2005-03-01 00:00:00