Abstract:
:Exact probability and likelihood computation on complex pedigrees is often infeasible, since exact methods are too computationally intensive even with today's computing technology. A statistical tool, Markov chain Monte Carlo (MCMC), is increasingly being explored as a technique for estimating probabilities of genotypic configurations on pedigrees conditional on phenotypic data. However, this conditional probability distribution on a complex pedigree is, in general, multimodal, and multimodality is one of the major difficulties in MCMC exploration of a probability surface. In this paper, a new member of the MCMC Metropolis-Hastings class of algorithms is proposed; the heated-Metropolis algorithm. The algorithm achieves passage through low probability states to other local modes of the probability distribution, and so provides much improved estimates of probabilities of interest. The example considered is the estimation of the probabilities of carrier genotype for the founders of a complex pedigree in which a very rare lethal recessive trait is segregating.
journal_name
Ann Hum Genetjournal_title
Annals of human geneticsauthors
Lin S,Thompson E,Wijsman Edoi
10.1111/j.1469-1809.1994.tb00731.xsubject
Has Abstractpub_date
1994-10-01 00:00:00pages
343-57issue
4eissn
0003-4800issn
1469-1809journal_volume
58pub_type
杂志文章abstract:INTRODUCTION:Limb-girdle muscular dystrophy (LGMD) is the fourth most common muscular dystrophy, with progressive proximal muscle weakness. However, a large number of neuromuscular conditions are similarly presented. Because of this, the use of high-throughput methods such as next-generation sequencing (NGS) is importa...
journal_title:Annals of human genetics
pub_type: 杂志文章
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更新日期:2019-09-01 00:00:00
abstract::Interaction between genetic variants is hypothesized to be one of several putative explanations for the 'case of missing heritability.' Therefore, Genome-Wide Interaction Analysis (GWIA) has recently gained substantial interest. GWIA is computationally challenging and respective power type I error studies are particul...
journal_title:Annals of human genetics
pub_type: 杂志文章
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abstract::In a landmark study Rosenberg et al. (2002) analyzed human genome diversity with 377 microsatellites in the HGDP-CEPH Genome Diversity Panel and reported that the populations were structured into five geographical regions: America, Sub-Saharan Africa, East Asia, Oceania and a cluster composed of Europe, the Middle Eas...
journal_title:Annals of human genetics
pub_type: 杂志文章
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更新日期:2006-09-01 00:00:00
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journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1046/j.1529-8817.2004.00095.x
更新日期:2004-07-01 00:00:00
abstract::The segregation of human cytosolic alanine aminotransferase (AAT1) and the individual human chromosomes has been studied in 27 secondary and tertiary rat hepatoma-human (liver) fibroblast hybrids. The staining solution used to visualize AAT activity on starch gels was specific for AAT since it was visualized only when...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.1982.tb00703.x
更新日期:1982-05-01 00:00:00
abstract::It is show that Wright's F-statistics can be defined as ratios of gene diversities of heterozygosities rather than as the correlations of uniting gametes. This definition is applicable irrespective of the number of alleles involved or whether there is selection or not. The relationship between F-statistics and Nei's g...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.1977.tb01918.x
更新日期:1977-10-01 00:00:00
abstract::It is often assumed that Afrikaners stem from a small number of Dutch immigrants. As a result they should be genetically homogeneous, show founder effects and be rather inbred. By disentangling my own South African pedigree, that is on average 12 generations deep, I try to quantify the genetic heritage of an Afrikaner...
journal_title:Annals of human genetics
pub_type: 杂志文章
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更新日期:2007-09-01 00:00:00
abstract::A crucial step beyond the identification of genetic linkage of a disease to a chromosomal region is the production of a physical map that will allow the identification of candidate genes. Although the process of physical map building has been facilitated by the flow of data released by the Human Genome Project, gather...
journal_title:Annals of human genetics
pub_type: 杂志文章,评审
doi:10.1017/S0003480001008594
更新日期:2001-05-01 00:00:00
abstract::Specific language impairment (SLI) is defined as an inability to develop appropriate language skills without explanatory medical conditions, low intelligence or lack of opportunity. Previously, a genome scan of 98 families affected by SLI was completed by the SLI Consortium, resulting in the identification of two quan...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.2007.00361.x
更新日期:2007-09-01 00:00:00
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journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.2007.00427.x
更新日期:2008-05-01 00:00:00
abstract::Appetite regulatory neural network and adipocyte homeostasis molecular pathways are critical to long-term weight maintenance. Associations between obesity-related phenotypes and four genes in these pathways - leptin (LEP), leptin receptor (LEPR), neuropeptide Y2 receptor (NPY2R) and peptide YY (PYY) were examined in C...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.2010.00596.x
更新日期:2010-09-01 00:00:00
abstract::Peripheral blood from six patients with Huntington's disease (HD) and six controls were cultured in three types of media known to produce fragile sites. A total of 3000 metaphases per group were scrutinized in a blind coded study. No significantly specific 'hot-spot' was found capable of differentiating between HD pat...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.1985.tb01704.x
更新日期:1985-10-01 00:00:00
abstract::The available simple mapping functions are surveyed, and a new mapping function that provides for positive interference within chromosome arms and no interference across the centromere is proposed, together with the corresponding formula for centromeric linkage. This new function is derived by assuming that all chromo...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.1976.tb00175.x
更新日期:1976-11-01 00:00:00
abstract::Q-banded chromosome 1 bivalents from six human males were measured in order to determine the locations of the major band borders. Chiasma position was also recorded in these bivalents in order to determine whether chiasmata preferentially occurred in Q-bright regions, Q-dark regions or in the interfaces between. The r...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.1985.tb01686.x
更新日期:1985-05-01 00:00:00
abstract::Statistical methods are developed for tracing quantitative measurements on human chromosomes from parents to offspring. Tests for transmission are briefly considered. ...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.1977.tb01963.x
更新日期:1977-07-01 00:00:00
abstract::A simple selection model (fitness 1, w, w2 for AA, Aa, aa) is employed to change the gene frequency of one population to another. The genetic distance is then defined as d = -log w between the two populations. The distance is symmetrical with respect to the two populations. It is additive: d13 = d12 + d23. The samplin...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.1978.tb00922.x
更新日期:1978-05-01 00:00:00
abstract::Serum alpha1 antitrypsin levels and phenotypes were examined in 1000 healthy adults in Northern Ireland. The Pi phenotype M accounted for 87-8% Pi MS for 7-3% and Pi MZ for 3-5%. The percentages of the rarer phenotypes were Pi FM 0-3, Pi IM 0-6, Pi SZ 0-4 and Pi Z--0-1. The range of alpha1 antitrypsin levels in differ...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.1975.tb00612.x
更新日期:1975-01-01 00:00:00
abstract::The index of opportunity for selection proposed by Crow has been calculated for the Italian population during the last century. The evolution of its two components, the pre-reproductive mortality and the variance in fertility, has been also analysed and compared with similar data for the United States. The results cle...
journal_title:Annals of human genetics
pub_type: 历史文章,杂志文章
doi:10.1111/j.1469-1809.1979.tb00671.x
更新日期:1979-01-01 00:00:00
abstract::Animal studies have shown that the peroxime proliferator-activated receptor delta (PPARD) gene regulates glucose metabolism and insulin sensitivity. Genetic variation in the PPARD gene might affect physical endurance and has been associated with obesity. We investigated the independent and modifying effect of variants...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.2011.00669.x
更新日期:2011-09-01 00:00:00
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journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.1996.tb01618.x
更新日期:1996-11-01 00:00:00
abstract::Here we report on a male infant presenting the typical pattern of Jacobsen syndrome including trigonocephaly, thrombocytopenia, congenital heart defect, urethral stenosis, and partial agenesis of the corpus callosum. Conventional karyotyping, FISH, SKY and CGH analyses showed that the region distal to the MLL locus on...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.2006.00271.x
更新日期:2006-11-01 00:00:00
abstract::For many complex diseases, study has suggested that the disease genes influence not only the occurrence of the disease, but also the age of onset. Current methods in linkage analysis are mainly concentrated on affected relative pairs or affected family members, and age of onset information is either ignored or is take...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1046/j.1469-1809.1998.6240323.x
更新日期:1998-07-01 00:00:00
abstract::Population samples from Liguria, Piacenza and Pavia provinces, and North Lombardy are compared for surnames and HLA gene frequencies. The genetic structure inferred from the principal coordinate analysis of surname frequencies is different from that inferred from HLA gene frequencies. The latter may represent ancient ...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1046/j.1469-1809.1998.6230261.x
更新日期:1998-05-01 00:00:00
abstract::In a Muslim Arab village, relatively isolated because of the preference of consanguineous marriages, we studied the fate of 12 mutations in 5 different genes. The study was based on carriers detected among relatives of affected patients and of carriers discovered in a random sample of 424 adults. Most of the mutations...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.2006.00308.x
更新日期:2007-03-01 00:00:00
abstract::Determination of activity and electrophoretic mobility of GALT in patients with various chromosome 9 deletions and duplications confirms the assignment of its locus to 9p and suggests its locus is in the segment 9cen leads to p22. Two inversions of 9qh (inv(9)(p11q12)) did not alter GALT expression. ...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.1980.tb01568.x
更新日期:1980-05-01 00:00:00
abstract::The routine performance of high-altitude (HA) natives in the hypoxic environment of HA exemplifies the process of adaptation mainly through natural selection. The recent therapeutic application of nitric oxide (NO) in HA disorders, for the improvement of oxygenation and vasodilation, ushered us to investigate the endo...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1046/j.1529-8817.2005.00158.x
更新日期:2005-05-01 00:00:00
abstract::Numerous functional studies have implicated PARL in relation to type 2 diabetes (T2D). We hypothesised that conflicting human association studies may be due to neighbouring causal variants being in linkage disequilibrium (LD) with PARL. We conducted a comprehensive candidate gene study of the extended LD genomic regio...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/ahg.12072
更新日期:2014-09-01 00:00:00
abstract::It has been shown that parametric analysis of linkage disequilibrium conditional on linkage using an overly deterministic model can be optimal for family-based association analysis. However, if one applies this strategy carelessly, there is a risk of false inference. We analyse properties of such likelihood ratio test...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.2011.00683.x
更新日期:2012-01-01 00:00:00
abstract::We set out to determine whether expansions in the C9ORF72 repeat found in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) families are associated with Parkinson disease (PD). We determined the repeat size in a total of 889 clinically ascertained patients (including PD and essential tremor plus Pa...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/ahg.12033
更新日期:2013-09-01 00:00:00
abstract::Data on Turner Syndrome from four sources were analysed for possible associations with several aetiological factors. Two classes of liveborn propositae were included, those with a non-mosaic 45, X karyotype (XO) and those with an isochromosome of the long arm of the X (iso-X). The numbers were 288 and 84 respectively ...
journal_title:Annals of human genetics
pub_type: 杂志文章
doi:10.1111/j.1469-1809.1980.tb01570.x
更新日期:1980-05-01 00:00:00