Abstract：
:False-positive or false-negative results attributable to undetected genotyping errors and confounding factors present a constant challenge for genome-wide association studies (GWAS) given the low signals associated with complex phenotypes and the noise associated with high-throughput genotyping. In the context of the genetics of kidneys in diabetes (GoKinD) study, we identify a source of error in genotype calling and demonstrate that a standard battery of quality-control (QC) measures is not sufficient to detect and/or correct it. We show that, if genotyping and calling are done by plate (batch), even a few DNA samples of marginally acceptable quality can profoundly alter the allele calls for other samples on the plate. In turn, this leads to significant differential bias in estimates of allele frequency between plates and, potentially, to false-positive associations, particularly when case and control samples are not sufficiently randomized to plates. This problem may become widespread as investigators tap into existing public databases for GWAS control samples. We describe how to detect and correct this bias by utilizing additional sources of information, including raw signal-intensity data.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Pluzhnikov A,Below JE,Konkashbaev A,Tikhomirov A,Kistner-Griffin E,Roe CA,Nicolae DL,Cox NJdoi
10.1016/j.ajhg.2010.06.005subject
Has Abstractpub_date
2010-07-09 00:00:00pages
123-8issue
1eissn
0002-9297issn
1537-6605pii
S0002-9297(10)00308-3journal_volume
87pub_type
杂志文章abstract：:Cellular DNAs from a panel of 20 unrelated individuals were screened for restriction fragment length polymorphisms (RFLP) with a DNA probe containing the first exon of the proopiomelanocortin gene (POMC), which has been assigned to chromosome 2p23-25. Digestion with the restriction endonuclease Sst 1 revealed a high f...
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：:Prenatal hemoglobinopathy screening was chosen as a model system for the study of patient receptivity to unsolicited genetic information. Providers of prenatal care in Rochester, NY, were offered free testing of all their prenatal patients and genetic counseling of women found positive. The 18,907 prenatal samples tes...
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：:Moyamoya disease is characterized by bilateral stenosis and/or occlusion of the terminal portion of the internal carotid artery. Moyamoya disease is prevalent among patients <10 years of age. Although most cases appear to be sporadic, approximately 10% occur as familial cases. The incidence of familial cases has been ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302243
更新日期：1999-02-01 00:00:00
abstract：:Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2008.08.002
更新日期：2008-09-01 00:00:00
abstract：:Some genes that affect development and behavior in mammals are known to be imprinted; and > or = 1% of all mammalian genes are imprinted. Hence, incorporating an imprinting parameter into linkage analysis may increase the power to detect linkage for these traits. Here we propose theoretical justifications for a recent...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/338931
更新日期：2002-03-01 00:00:00
abstract：:Charcot-Marie-Tooth disease is characterized by length-dependent axonal degeneration with distal sensory loss and weakness, deep-tendon-reflex abnormalities, and skeletal deformities. It is caused by mutations in more than 40 genes. We investigated a four-generation family with 23 members affected by the axonal form (...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2011.07.002
更新日期：2011-08-12 00:00:00
abstract：:EXTL3 regulates the biosynthesis of heparan sulfate (HS), important for both skeletal development and hematopoiesis, through the formation of HS proteoglycans (HSPGs). By whole-exome sequencing, we identified homozygous missense mutations c.1382C>T, c.1537C>T, c.1970A>G, and c.2008T>G in EXTL3 in nine affected individ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2017.01.013
更新日期：2017-02-02 00:00:00
abstract：:Myotonic dystrophy (DM) is a progressive neuromuscular disorder which results from elongations of an unstable (CTG)n repeat, located in the 3' untranslated region of the DM gene. A correlation has been demonstrated between the increase in the repeat number of this sequence and the severity of the disease. However, the...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-05-01 00:00:00
abstract：:On the basis of accumulating evidence that obesity has a substantial genetic component, a genomewide search for linkages of DNA markers to percent body fat is ongoing in Pima Indians, a population with a very high prevalence of obesity. An initial screen of the genome (>600 markers in 874 individuals) has been complet...
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：:We tested 519 chromosome 3-specific cosmids for the presence of rare restriction-endonuclease sites in a search for cosmids containing HTF islands. We have identified 49 cosmids (9% of those tested) that contain multiple rare restriction-endonuclease sites. The cosmids were digested with several common cutting restric...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-09-01 00:00:00
abstract：:SOX6 belongs to a family of 20 SRY-related HMG-box-containing (SOX) genes that encode transcription factors controlling cell fate and differentiation in many developmental and adult processes. For SOX6, these processes include, but are not limited to, neurogenesis and skeletogenesis. Variants in half of the SOX genes ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2020.04.015
更新日期：2020-06-04 00:00:00
abstract：:In spondylocostal dysostosis (SD), vertebral-segmentation defects are associated with rib anomalies. This results in short-trunk short stature, nonprogressive kyphoscoliosis, and radiological features of multiple hemivertebrae and rib fusions. SD can be familial, and both autosomal dominant and autosomal recessive (AR...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302464
更新日期：1999-07-01 00:00:00
abstract：:The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2007.12.011
更新日期：2008-03-01 00:00:00
abstract：:An astonishing amount of behavioral variation is captured within the more than 350 breeds of dog recognized worldwide. Inherent in observations of dog behavior is the notion that much of what is observed is breed specific and will persist, even in the absence of training or motivation. Thus, herding, pointing, trackin...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：10.1016/j.ajhg.2007.12.001
更新日期：2008-01-01 00:00:00
abstract：:Mucopolysaccharidosis type I (MPS-I) is an autosomal recessive genetic disease caused by a deficiency of the lysosomal glycosidase alpha-L-iduronidase. Hurler (severe), Scheie (mild), and Hurler/Scheie (intermediate) syndromes are clinical subtypes of MPS-I, but it is difficult to distinguish between these subtypes by...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-11-01 00:00:00
abstract：:A black family with two male infants affected with the X-linked Lowe syndrome was studied. All three females in the pedigree were found to be carriers on the basis of lenticular opacities. Each female had one son. Of these, two were affected and one was unaffected. The Xg blood-group locus and the G6PD locus were dete...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1982-11-01 00:00:00
abstract：:Alternative splicing is a tightly regulated biological process by which the number of gene products for any given gene can be greatly expanded. Genomic variants in splicing regulatory sequences can disrupt splicing and cause disease. Recent developments in sequencing technologies and computational biology have allowed...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：10.1016/j.ajhg.2017.11.002
更新日期：2018-01-04 00:00:00
abstract：:D1S1, a human anonymous DNA clone originally called lambda Ch4A-H3 or lambda H3, was mapped by two other laboratories to human chromosome 1p36 by in situ hybridization but its localization was not confirmed using a different mapping method. We used a panel of human-hamster somatic cell hybrids to show that there are c...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-04-01 00:00:00
abstract：:Fibroblast cultures from 12 unrelated patients with classical Menkes disease were analyzed for mutations in the MNK gene, by reverse transcription-PCR (RT-PCR) and chemical cleavage mismatch detection. Mutations were observed in 10 patients, and in each case a different mutation was present. All of the mutations would...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-11-01 00:00:00
abstract：:Recent advances in genome technology have led to mapping and subsequent isolation, by positional cloning, of a number of genes for common and/or complex human diseases. It therefore will be possible to utilize information about a known locus in the search for additional, perhaps less penetrant, genes for a particular ...
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：:Down syndrome (DS) is the most common cause of mental retardation. Many neural phenotypes are shared between DS individuals and DS mouse models; however, the common underlying molecular pathogenetic mechanisms remain unclear. Using a transchromosomic model of DS, we show that a 30%-60% reduced expression of Nrsf/Rest ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2008.08.012
更新日期：2008-09-01 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：:Uniparental disomy (UPD) is a rare condition in which a diploid offspring carries a chromosomal pair from a single parent. We now report the first two cases of UPD resulting in retinal degeneration. We identified an apparently homozygous loss-of-function mutation of RPE65 (1p31) in one retinal dystrophy patient and an...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/338455
更新日期：2002-01-01 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：:Genomic rearrangements involving the peripheral myelin protein gene (PMP22) in human chromosome 17p12 are associated with neuropathy: duplications cause Charcot-Marie-Tooth disease type 1A (CMT1A), whereas deletions lead to hereditary neuropathy with liability to pressure palsies (HNPP). Our previous studies showed th...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.05.001
更新日期：2010-06-11 00:00:00
abstract：:To better define the nature of FMR1 CGG-repeat expansions, changes in allele sizes for 191 families with fragile X and for 33 families with gray-zone repeats (40-60) were analyzed. Expansion of the fragile X chromosome to the full mutation was seen in 13.4% of offspring from premutation mothers with 56-59 repeats, 20....
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:Congenital universal muscular hypoplasia has been confused with similar diseases in the past. Evidence presented in this paper distinguishes this disorder from other phenotypically similar ones and indicates that it is inherited as an autosomal recessive disorder. ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1979-09-01 00:00:00
abstract：:Isolated complex I deficiency is a common biochemical phenotype observed in pediatric mitochondrial disease and often arises as a consequence of pathogenic variants affecting one of the ∼65 genes encoding the complex I structural subunits or assembly factors. Such genetic heterogeneity means that application of next-g...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2018.08.013
更新日期：2018-10-04 00:00:00
abstract：:Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is a rare, multisystem disorder characterized clinically by ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility, leukoencephalopathy, thin body habitus, and myopathy. Laboratory studies reveal defects of oxidative-phosphoryla...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301979
更新日期：1998-08-01 00:00:00
abstract：:Autosomal dominant progressive external ophthalmoplegia (adPEO) is a disorder characterized by ptosis, progressive weakness of the external eye muscles, and general muscle weakness. The patients have multiple deletions of mtDNA on Southern blots or in PCR analysis of muscle DNA and a mild deficiency of one or more res...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-04-01 00:00:00
