Abstract：
:The identification of genes associated with hereditary disorders has contributed to improving medical care and to a better understanding of gene functions, interactions, and pathways. However, there are well over 1500 Mendelian disorders whose molecular basis remains unknown. At present, methods such as linkage analysis can identify the chromosomal region in which unknown disease genes are located, but the regions could contain up to hundreds of candidate genes. In this work, we present a method for prioritization of candidate genes by use of a global network distance measure, random walk analysis, for definition of similarities in protein-protein interaction networks. We tested our method on 110 disease-gene families with a total of 783 genes and achieved an area under the ROC curve of up to 98% on simulated linkage intervals of 100 genes surrounding the disease gene, significantly outperforming previous methods based on local distance measures. Our results not only provide an improved tool for positional-cloning projects but also add weight to the assumption that phenotypically similar diseases are associated with disturbances of subnetworks within the larger protein interactome that extend beyond the disease proteins themselves.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Köhler S,Bauer S,Horn D,Robinson PNdoi
10.1016/j.ajhg.2008.02.013subject
Has Abstractpub_date
2008-04-01 00:00:00pages
949-58issue
4eissn
0002-9297issn
1537-6605pii
S0002-9297(08)00172-9journal_volume
82pub_type
杂志文章abstract：:Four subjects with thermolabile methylenetetrahydrofolate reductase (MTHFR) were discovered among 16 "obligate" heterozygotes for severe MTHFR deficiency and their family members. All four subjects had less than 25% of normal mean MTHFR specific activity in lymphocyte extracts. Three of them with normal serum folate a...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-03-01 00:00:00
abstract：:The first hypervariable segment of the human mtDNA control region contains a homopolymeric tract of cytosines between nt 16184 and 16193, interrupted at position 16189 by a thymine, according to the Cambridge reference sequence. A variant commonly found in population screening is a T-to-C transition at nt 16189, resul...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:In Williams syndrome (WS), a deletion of approximately 1.5 Mb on one copy of chromosome 7 causes specific physical, cognitive, and behavioral abnormalities. Molecular dissection of the phenotype may be a route to identification of genes important in human cognition and behavior. Among the genes known to be deleted in ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302214
更新日期：1999-01-01 00:00:00
abstract：:A rare germ-line polymorphism in codon 47 of the p53 gene replaces the wild-type proline (CCG) with a serine (TCG). Restriction analysis of 101 human samples revealed the frequency of the rare allele to be 0% (n = 69) in Caucasians and 4.7% (3/64, n = 32) among African-Americans. To investigate the consequence of this...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-09-01 00:00:00
abstract：:Family studies of schizophrenia have reported elevated rates of both definite and definite-plus-probable schizophrenia among the relatives of definite schizophrenics. These elevated rates imply a strong association between the two forms of diagnosis and suggest some form of familial transmission. Here we have used rec...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1983-11-01 00:00:00
abstract：:Insulin resistance and hyperinsulinemia are strong correlates of obesity and type 2 diabetes, but little is known about their genetic determinants. Using data on nondiabetics from Mexican American families and a multipoint linkage approach, we scanned the genome and identified a major locus near marker D6S403 for fast...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/320100
更新日期：2001-05-01 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：:We demonstrate that satellite III (SatIII) DNA subfamilies cloned from human acrocentric chromosomes arose in the Hominoidea superfamily. Two groups, distinguished by sequence composition, evolved nonconcurrently, with group 2 evolving 16-23 million years ago (MYA) and the more recent group 1 sequences emerging approx...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/512132
更新日期：2007-03-01 00:00:00
abstract：:DNA was extracted from the skeletal remains of 62 specimens excavated from the Egyin Gol necropolis, in northern Mongolia. This burial site is linked to the Xiongnu period and was used from the 3rd century b.c. to the 2nd century a.d. Three types of genetic markers were used to determine the genetic relationships betw...
journal_title：American journal of human genetics
pub_type： 历史文章,杂志文章
doi：10.1086/377005
更新日期：2003-08-01 00:00:00
abstract：:The genetic locus for facioscapulohumeral muscular dystrophy (FSHD) has been mapped to chromosome 4. We have examined linkage to five chromosome 4q DNA markers in 22 multigenerational FSHD families. Multipoint linkage analyses of the segregation of four markers in the FSHD families and in 40 multigenerational mapping ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1992-08-01 00:00:00
abstract：:Autism is a heritable but genetically complex disorder characterized by deficits in language and in reciprocal social interactions, combined with repetitive and stereotypic behaviors. As with many genetically complex disorders, numerous genome scans reveal inconsistent results. A genome scan of 345 families from the A...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/430278
更新日期：2005-06-01 00:00:00
abstract：:Assignment of alleles to haplotypes for nearly all the variants on all chromosomes can be performed by genetic analysis of a nuclear family with three or more children. Whole-genome sequence data enable deterministic phasing of nearly all sequenced alleles by permitting assignment of recombinations to precise chromoso...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2011.07.023
更新日期：2011-09-09 00:00:00
abstract：:We present methods for linkage and association mapping of quantitative traits for a founder population with a large, known genealogy. We detect linkage to quantitative-trait loci (QTLs) through a multipoint homozygosity-mapping method. We propose two association methods, one of which is single point and uses a general...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/339705
更新日期：2002-04-01 00:00:00
abstract：:Assignment of a susceptibility locus for cutaneous malignant melanoma-dysplastic nevus (CMM/DN) to chromosome 1p remains controversial. We examined the relationship between CMM/DN and markers D1S47, PND, and D1S160 on seven new families (set B) plus updated versions of six previously reported families (set A). Three l...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-03-01 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：:The genetic linkage of the loci for lymphocyte cytosol polypeptide with molecular weight of 64,000 (LCP1) and esterase (ESD) were examined by two-dimensional gel electrophoresis using blood from four informative families. No recombinants were observed in the four families totaling 17 children, giving a summed lod scor...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1985-11-01 00:00:00
abstract：:A genomewide screen for quantitative-trait loci (QTLs) that underlie asthma was performed on 533 Chinese families with asthma, by the unified Haseman-Elston method. Nine asthma-related phenotypes were studied, including forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), airway responsiveness as indic...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/324650
更新日期：2001-12-01 00:00:00
abstract：:Eighty unrelated individuals with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) were found to have deletions in the major deletion-rich region of the DMD locus. This region includes the last five exons detected by cDNA5b-7, all exons detected by cDNA8, and the first two exons detected by cDNA9. ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
abstract：:Attention-deficit hyperactivity disorder (ADHD) has been shown to be familial and heritable, in previous studies. As with most psychiatric disorders, examination of pedigrees has not revealed a consistent Mendelian mode of transmission. The response of ADHD patients to medications that inhibit the dopamine transporter...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:Huntington disease (HD) is a dominantly inherited neurodegenerative disorder characterized by dysregulation of various genes. Recently, microRNAs (miRNAs) have been reported to be involved in this dysregulation, suggesting that manipulation of appropriate miRNA regulation may have a therapeutic benefit. Here, we repor...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.05.025
更新日期：2013-08-08 00:00:00
abstract：:We describe a maternally transmitted genomic-imprinting syndrome of mental retardation, hypotonia, and unique dysmorphism with elongated face. We mapped the disease-associated locus to approximately 7.27 Mb on chromosome 8q24 and demonstrated that the disease is caused by a missense mutation in the maternal copy of KC...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2008.07.010
更新日期：2008-08-01 00:00:00
abstract：:Pc 1 Duarte is a mutant brain protein present in 32% of the normal human population with 2.6% being homozygous. Preliminary studies suggest an increased frequency of this mutation in individuals with affective disease. To determine if this mutant was present in primates, 32 fetal (wild)-born baboons were examined. All...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1981-01-01 00:00:00
abstract：:We present the findings of a large linkage study of bipolar affective disorder (BPAD) that involved genomewide analysis of 52 families (448 genotyped individuals) of Spanish, Romany, and Bulgarian descent and further fine mapping of the 1p34-p36, 4q28-q31, and 6q15-q24 regions. An additional sample of 56 German famili...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/498619
更新日期：2005-12-01 00:00:00
abstract：:X-linked retinitis pigmentosa (XLRP) is a clinically and genetically heterogeneous degenerative disease of the retina. At least five loci have been mapped for XLRP; of these, RP2 and RP3 account for 10%-20% and 70%-90% of genetically identifiable disease, respectively. However, mutations in the respective genes, RP2 a...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/340848
更新日期：2002-06-01 00:00:00
abstract：:Linkage is a phenomenon that correlates the genotypes of loci, rather than the phenotypes of one locus to the genotypes of another. It is therefore necessary to convert the observed trait phenotypes into trait-locus genotypes, which can then be analyzed for coinheritance with marker-locus genotypes. However, if the mo...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302797
更新日期：2000-03-01 00:00:00
abstract：:Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2011.10.002
更新日期：2011-11-11 00:00:00
abstract：:The problem considered is that of estimating the age or rate of increase of a variant on the basis of the present number of replicates observed in a population. In place of previous diffusion equation analyses of age probability distributions, the likelihood for the age is studied on the basis of a discrete branching ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1976-09-01 00:00:00
abstract：:We have devised a zymogram method with high sensitivity and resolution for investigating molecular heterogeneity and genetic polymorphism of deoxyribonuclease I. A combination technique of polyacrylamide-gel isoelectric-focusing electrophoresis and the newly developed zymogram method have led to the discovery of genet...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-07-01 00:00:00
abstract：:Association studies offer an exciting approach to finding underlying genetic variants of complex human diseases. However, identification of genetic variants still includes difficult challenges, and it is important to develop powerful new statistical methods. Currently, association methods may depend on single-locus an...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/511312
更新日期：2007-02-01 00:00:00
abstract：:A gene for Holt-Oram syndrome (HOS) has been previously mapped to chromosome 12q2 and designated HOS1. We have identified a HOS patient with a de novo chromosomal rearrangement involving 12q. Detailed cytogenetic analysis of this case reveals three breaks on 12q, and two of these are within the HOS1 interval. By using...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
