Abstract：
:Linkage analysis using maximum-likelihood estimation is a powerful tool for locating genes. As available data sets have grown, the computation required for analysis has grown exponentially and become a significant impediment. Others have previously shown that parallel computation is applicable to linkage analysis and can yield order-of-magnitude improvements in speed. In this paper, we demonstrate that algorithmic modifications can also yield order-of-magnitude improvements, and sometimes much more. Using the software package LINKAGE, we describe a variety of algorithmic improvements that we have implemented, demonstrating both how these techniques are applied and their power. Experiments show that these improvements speed up the programs by an order of magnitude, on problems of moderate and large size. All improvements were made only in the combinatorial part of the code, without restoring to parallel computers. These improvements synthesize biological principles with computer science techniques, to effectively restructure the time-consuming computations in genetic linkage analysis.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Cottingham RW Jr,Idury RM,Schäffer AAsubject
Has Abstractpub_date
1993-07-01 00:00:00pages
252-63issue
1eissn
0002-9297issn
1537-6605journal_volume
53pub_type
杂志文章abstract：:Monosomy for the X chromosome in humans creates a genetic Achilles' heel for nature to deal with. We report that the human X chromosome appears to have one-third the density of the coding sequence of the autosomes and, because of partial shielding from the high mutation rate of the male sex, that it should also have a...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/303010
更新日期：2000-08-01 00:00:00
abstract：:Beta-Glucosidase activity measured by synthetic substrate at pH 4.6 was low in the cultured amniotic cells from two pregnant women at risk for juvenile and adult type Gaucher disease. The diagnosis was confirmed by showing a low activity of beta-glucosidase in the skin fibroblasts with a synthetic substrate or in the ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1978-05-01 00:00:00
abstract：:The Huntington disease (HD) gene has been mapped to the most distal subband of chromosome 4p. Analysis of recombination events has not provided an unequivocal location of the HD gene, but it indicates a position very close to the telomere as one possibility. We have constructed a yeast artificial chromosome (YAC) vect...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-04-01 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：:Triplets of the form of purine, purine, pyrimidine (RRY(i)) are enhanced in frequency in the genomes of primates, rodents, and bacteria. Some RRY(i) are "cryptic" repeats (cRRY(i)) in which no one tandem run of a trinucleotide predominates. A search of human GenBank sequence revealed that the sequences of cRRY(i) are ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
abstract：:Tibetan high-altitude adaptation (HAA) has been studied extensively, and many candidate genes have been reported. Subsequent efforts targeting HAA functional variants, however, have not been that successful (e.g., no functional variant has been suggested for the top candidate HAA gene, EPAS1). With WinXPCNVer, a metho...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2015.05.005
更新日期：2015-07-02 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：:Parkinson disease (PD) is a common neurodegenerative disorder caused by environmental and genetic factors. We have previously shown linkage of PD to chromosome 8p. Subsequently, fibroblast growth factor 20 (FGF20) at 8p21.3-22 was identified as a risk factor in several association studies. To identify the risk-conferr...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2007.09.021
更新日期：2008-02-01 00:00:00
abstract：:Shprintzen-Goldberg syndrome (SGS) is characterized by severe marfanoid habitus, intellectual disability, camptodactyly, typical facial dysmorphism, and craniosynostosis. Using family-based exome sequencing, we identified a dominantly inherited heterozygous in-frame deletion in exon 1 of SKI. Direct sequencing of SKI ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.10.002
更新日期：2012-11-02 00:00:00
abstract：:Studies in mouse and chick have shown that the 5' HoxD genes play major roles in the development of the limbs and genitalia. In humans, mutations in HOXD13 cause the dominantly inherited limb malformation synpolydactyly (SPD). Haploinsufficiency for the 5' HOXD genes has recently been proposed to underlie the monodact...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/338921
更新日期：2002-02-01 00:00:00
abstract：:Protoporphyria is an autosomal dominant disease in man in which protoporphyrin accumulated because of a defect in heme synthase (ferrochelatase) activity. A disease has been described in cattle that has the same manifestations as does the human disease. We measured heme synthase activity in sonicates of cultured skin ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1982-03-01 00:00:00
abstract：:Misspecification of transmission model parameters can produce artifactually negative lod scores at small recombination fractions and in multipoint analysis. To avoid this problem, we have tried to devise a test that aims to detect a genetic effect at a particular locus, rather than attempting to estimate the map posit...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-09-01 00:00:00
abstract：:Deletions of chromosome 1p36 affect approximately 1 in 5,000 newborns and are associated with developmental delay, intellectual disability, and defects involving the brain, eye, ear, heart, and kidney. Arginine-glutamic acid dipeptide repeats (RERE) is located in the proximal 1p36 critical region. RERE is a widely-exp...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2016.03.002
更新日期：2016-05-05 00:00:00
abstract：:To investigate the molecular basis for the distinct neuronopathic phenotypes of Gaucher disease, acid beta-glucosidases expressed from mutant DNAs in Gaucher disease type 2 (acute) and type 3 (subacute) patients were characterized in fibroblasts and with the baculovirus expression system in insect cells. Expression of...
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：:Multiple-synostosis syndrome is an autosomal dominant disorder characterized by progressive symphalangism, carpal/tarsal fusions, deafness, and mild facial dysmorphism. Heterozygosity for functional null mutations in the NOGGIN gene has been shown to be responsible for the disorder. However, in a cohort of six proband...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/503204
更新日期：2006-04-01 00:00:00
abstract：:The highly polymorphic locus D2S3 is revealed by three single-copy probes from cosmid C1-5. These probes, 1-30, 1-32, and 2-96, collectively reveal seven restriction fragment length polymorphisms. Fifty-three of 56 unrelated individuals (93%) were heterozygous at one or more of the seven loci, making the compound locu...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
abstract：:Despite the growing consensus on the importance of testing gene-gene interactions in genetic studies of complex diseases, the effect of gene-gene interactions has often been defined as a deviance from genetic additive effects, which is essentially treated as a residual term in genetic analysis and leads to low power i...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/508571
更新日期：2006-11-01 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：:The gene that is involved in juvenile neuronal ceroid lipofuscinosis (JNCL), or Batten disease--CLN3--has been localized to 16p12, and the mutation shows a strong association with alleles of microsatellite markers D16S298, D16S299, and D16S288. Recently, haplotype analysis of a Batten patient from a consanguineous rel...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-03-01 00:00:00
abstract：:Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and i...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2020.07.006
更新日期：2020-09-03 00:00:00
abstract：:Familial juvenile polyposis (FJP) is a hamartomatouspolyposis syndrome in which affected family members develop upper and lower gastrointestinal juvenile polyps and are at increased risk for gastrointestinal cancer. A genetic locus for FJP has not yet been identified by linkage; therefore, the objective of this study ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/301840
更新日期：1998-05-01 00:00:00
abstract：:A four-generation Swedish family with a new type of X-linked mental retardation syndrome was recently reported by Gustavson et al. The complex syndrome includes microcephaly, severe mental retardation, optical atrophy with decreased vision or blindness, severe hearing defect, characteristic facial features, spasticity...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-06-01 00:00:00
abstract：:Methylmalonyl CoA mutase (MCM) catalyzes an essential step in the degradation of several branch-chain amino acids and odd-chain fatty acids. Deficiency of this apoenzyme causes the mut form of methylmalonic acidemia, an often fatal disorder of organic acid metabolism. An MCM cDNA has recently been obtained from human ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
abstract：:The structural gene for the human lysosomal enzyme aspartylglucosaminidase (AGA) has been assigned to chromosome 4 using somatic cell hybridization techniques. The human monomeric enzyme was detected in Chinese hamster-human cell hybrids by a thermal denaturation assay that selectively inactivated the Chinese hamster ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1984-11-01 00:00:00
abstract：:Although intensive efforts have been undertaken to elucidate the genetic background of immunoglobulin A nephropathy (IgAN), genetic factors associated with the pathogenesis of this disease are still not well understood. We designed a case-control association study that was based on linkage disequilibrium among single-...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/339077
更新日期：2002-03-01 00:00:00
abstract：:The still debated question of whether the expression of mental retardation in heterozygous carriers of the Martin-Bell syndrome is influenced by X inactivation has been investigated in a group of phase-known double heterozygotes for the FRA-X mutant and the G6PD Mediterranean variant. In these individuals, the number ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-04-01 00:00:00
abstract：:Genetic and environmental influences on systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial blood pressure (MBP) were examined in 371 French-Canadian families by using path analysis. Familial environment was estimated with environmental indices constructed from as many as 14 (of a pool of ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-08-01 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：:Hereditary hemorrhagic telangiectasia (HHT), the most common inherited vascular disorder, is caused by mutations in genes involved in the transforming growth factor beta (TGF-β) signaling pathway (ENG, ACVRL1, and SMAD4). Yet, approximately 15% of individuals with clinical features of HHT do not have mutations in thes...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.07.004
更新日期：2013-09-05 00:00:00
abstract：:When population geneticists wish to determine the genetic consequences of some aspect of mating behavior, it is often necessary to compare observed levels of consanguinity to the level expected when mating is random with respect to the factor being studied. Expectations under random mating are often derived from discr...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
