Abstract：
:Many recent studies have established that haplotype diversity in a small region may not be greatly diminished when the number of markers is reduced to a smaller set of "haplotype-tagging" single-nucleotide polymorphisms (SNPs) that identify the most common haplotypes. These studies are motivated by the assumption that retention of haplotype diversity assures retention of power for mapping disease susceptibility by allelic association. Using two bodies of real data, three proposed measures of diversity, and regression-based methods for association mapping, we found no scenario for which this assumption was tenable. We compared the chi-square for composite likelihood and the maximum chi-square for single SNPs in diplotypes, excluding the marker designated as causal. All haplotype-tagging methods conserve haplotype diversity by selecting common SNPs. When the causal marker has a range of allele frequencies as in real data, chi-square decreases faster than under random selection as the haplotype-tagging set diminishes. Selecting SNPs by maximizing haplotype diversity is inefficient when their frequency is much different from the unknown frequency of the causal variant. Loss of power is minimized when the difference between minor allele frequencies of the causal SNP and a closely associated marker SNP is small, which is unlikely in ignorance of the frequency of the causal SNP unless dense markers are used. Therefore retention of haplotype diversity in simulations that do not mirror genomic allele frequencies has no relevance to power for association mapping. TagSNPs that are assigned to bins instead of haplotype blocks also lose power compared with random SNPs. This evidence favours a multi-stage design in which both models and density change adaptively.
journal_name
Hum Genetjournal_title
Human geneticsauthors
Zhang W,Collins A,Morton NEdoi
10.1007/s00439-004-1122-xkeywords:
subject
Has Abstractpub_date
2004-07-01 00:00:00pages
157-64issue
2eissn
0340-6717issn
1432-1203journal_volume
115pub_type
杂志文章相关文献
HUMAN GENETICS文献大全abstract：:We have investigated the origin of rapidly adhering (RA) cells in three cases of neural tube defects (two anencephali, one encephalocele). We were able to demonstrate the presence of glial fibrillary acidic (GFA) protein in variable percentages (4--80%) of RA cells cultured for 4--6 days by use of indirect immunofluor...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00274694
更新日期：1981-01-01 00:00:00
abstract：:The sex of a conceptus at the early embryonic state was diagnosed in 1000 induced abortions. Specimens were obtained from women who terminated their pregnancies within 12 menstrual weeks on socio-economic indications. By making use of the triple checking procedures, such as the karyotypic analysis of Giemsa-stained sl...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00446275
更新日期：1977-05-10 00:00:00
abstract：:Deletions in 17q11.2 affecting the NF1 gene and surrounding regions occur in 5% of patients with NF1. The two major types of NF1 deletions encompass 1.4-Mb and 1.2-Mb, respectively, and have breakpoints in the NF1 low-copy repeats or in the JJAZ gene and its pseudogene. Deletions larger than 1.4-Mb are rare, and only ...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/s00439-005-1265-4
更新日期：2005-05-01 00:00:00
abstract：:Enzymatic DNA amplification and polyacrylamide gel electrophoresis, which demonstrate different sizes of DNA fragments, were used to detect the common mutations causing beta-thalassemia and hemoglobin (Hb) E in Thai people. The 4-bp deletion at codons 41 and 42 can be detected directly by polyacrylamide gel electropho...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00274004
更新日期：1989-07-01 00:00:00
abstract：:A method based on a combination of cell culture and pharmacokinetic data is explored as a way of estimating the possible genetic risk to man from a mutagenic chemical. 8-methoxypsoralen, which is given to psoriasis patients as part of a photochemotherapy regime, is used, since it represents a 'real-life' situation and...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00277690
更新日期：1979-05-23 00:00:00
abstract：:After an association between genetic variants and a phenotype has been established, further study goals comprise the classification of patients according to disease risk or the estimation of disease probability. To accomplish this, different statistical methods are required, and specifically machine-learning approache...
journal_title：Human genetics
pub_type： 杂志文章,评审
doi：10.1007/s00439-012-1194-y
更新日期：2012-10-01 00:00:00
abstract：:Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is one of the most common autosomal recessive disorders and occurs in its non-classical form in up to 6% of hirsute women. We report on a young woman with the clinical diagnosis of non-classical CAH and a novel, heterozygous missense mutation CTG-->...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/s00439-005-1339-3
更新日期：2005-10-01 00:00:00
abstract：:Swiss albino male mice were administered two doses (1 and 2 HA units) of influenza A2 Hong Kong/68 virus IP. The incidence of chromosomal anomalies in spermatocytes was analysed at various times post infection and was found to be significantly higher than in controls, indicating that the influenza virus had induced th...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00286960
更新日期：1978-12-18 00:00:00
abstract：:Linkage analysis of 15 families affected by X-linked agammaglobulinaemia (XLA) showed close linkage with three probes located towards the centre of the long arm of the X chromosome. No cross-overs were found using pXG12 (DXS94) lod 6.6 or S21 (DXS17) lod 4.4. One cross-over was found with 19.2 (DXS3). This confirms an...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00272387
更新日期：1987-10-01 00:00:00
abstract：:Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disorder of unknown etiology and unclear pathogenesis. Matrix metalloproteinase-1 (MMP-1) is strongly upregulated and may contribute to the abnormal remodeling that characterizes the disease. We conducted a case-control study of 130 IPF pat...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/s00439-008-0571-z
更新日期：2008-12-01 00:00:00
abstract：:Two cases of trisomy 21q223 with the Down's phenotype were analysed by in situ hybridization with specific probes previously located in the sub-bands 21q221 (SOD-A) and 21q223 (BCEI and COL6A). These studies give evidence that the clinical picture of Down's syndrome is at least to a great extent correlated with trisom...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF01790097
更新日期：1988-11-01 00:00:00
abstract：:As evidenced by a large pedigree with 21 affected members, acrokeratoelastoidosis (AKE) is an autosomal dominant skin disease (10185; McKusick 1978). Linkage with genetic markers already assigned to human chromosomes could help to map the gene for this disease. Therefore 22 markers were investigated in 61 members of t...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00284653
更新日期：1983-01-01 00:00:00
abstract：:The size and position of the heterochromatic regions of chromosome 9 were examined in a group of women with histories of recurrent miscarriage and a control group of fertile women. Measurements were made on whole chromosomes (variability between chromosomes was taken to reflect differences in heterochromatin), and cor...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00276601
更新日期：1982-01-01 00:00:00
abstract：:Human tumor cells, after x-irradiation during the G2 phase of the cell cycle, show an abnormally high frequency of persistent chromatid breaks and gaps resulting from deficient DNA repair. Addition of a single human chromosome 11 from normal fibroblasts by micro-cell fusion to cell lines from six different tumors resu...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00219338
更新日期：1992-03-01 00:00:00
abstract：:Steroid 21-hydroxylase deficiency is the major cause of congenital adrenal hyperplasia. Genotyping for deletions and nine point mutations in the CYP21 gene has been performed in 38 Spanish patients and their relatives by Southern blot analysis and allele-specific oligonucleotide hybridization. Three clinical variants ...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00207379
更新日期：1995-08-01 00:00:00
abstract：:Few studies have examined the association of SNPs in the adiponectin (ADIPOQ) and adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) genes with the euglycemic clamp, i.e. the gold standard measure of insulin sensitivity. The association of comprehensive tag SNPs in these genes with insulin sensitivity was examined in a c...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/s00439-008-0595-4
更新日期：2009-02-01 00:00:00
abstract：:Three human chromosome 9-specific cosmid recombinants containing (CA)n microsatellites are described. Three microsatellite loci, D9S970, D9S971, and D9S972, were observed to have heterozygosities of 0.78, 0.84, and 0.82, respectively. Subchromosomal localizations were determined by R-banding and fluorescence in situ h...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00207389
更新日期：1995-08-01 00:00:00
abstract：:The association between trisomy 21 and a high incidence of atrioventricular canal defects (AVCDs) indicates that a locus on chromosome 21 is involved in this congenital heart defect. We have investigated whether a genetic locus on chromosome 21 is also involved in familial nonsyndromic AVCDs. Short tandem repeat polym...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00210591
更新日期：1994-02-01 00:00:00
abstract：:Defective function of the Sonic Hedgehog (SHH) signaling pathway is the most frequent alteration underlying holoprosencephaly (HPE) or its various clinical microforms. We performed an extensive mutational analysis of the entire human DISP1 gene, required for secretion of all hedgehog ligand(s) and which maps to the HP...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/s00439-009-0628-7
更新日期：2009-05-01 00:00:00
abstract：:The development of prenatal diagnosis in Italy was made difficult by the restrictions of the old abortion law and only in recent years has a consistent number of cases been investigated. We report the experience on prenatal chromosome diagnosis of ten Italian centers participating in a collaborative study on 4952 diag...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00281266
更新日期：1982-01-01 00:00:00
abstract：:Southern African Bantu-speaking negroid and San populations were examined with regard to the glucose-6-phosphate dehydrogenase (G6PD) PvuII restriction fragment length polymorphism (RFLP) showing alleles of 4 kb and 1.6 kb, called Type 1 and Type 2, respectively. The standardized disequilibrium coefficient for the ele...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00207056
更新日期：1992-04-01 00:00:00
abstract：:Chromosomal studies of the bone marrow and cultured peripheral blood cells in a 42-year-old female with the clinical and laboratory features typical for CML revealed a previously undescribed variant translocation involving chromosomes 12 and 22. ...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00287017
更新日期：1977-11-10 00:00:00
abstract：:Restriction endonucleases have been recently proved to be active on fixed chromosomes, thus they are useful in chromatin structure studies. Within this class of enzymes, Alu I is able to detect the presence and localization of highly repetitive DNA sequences in human and in other mammalian and dipteran species. In thi...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00291894
更新日期：1986-03-01 00:00:00
abstract：:Deficiency of liver arginase (AI) is characterized clinically by hyperargininemia, progressive mental impairment, growth retardation, spasticity, and periodic episodes of hyperammonemia. The rarest of the inborn errors of urea cycle enzymes, it has been considered the least life-threatening, by virtue of the typical a...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00230212
更新日期：1993-03-01 00:00:00
abstract：:The most frequent recurring mutations in neurofibromatosis type 1 (NF1) are large deletions encompassing the NF1 gene and its flanking regions (NF1 microdeletions). The majority of these deletions encompass 1.4-Mb and are associated with the loss of 14 protein-coding genes and four microRNA genes. Patients with germli...
journal_title：Human genetics
pub_type： 杂志文章,评审
doi：10.1007/s00439-017-1766-y
更新日期：2017-04-01 00:00:00
abstract：:rRNA gene activity was evaluated by cytologic methods in cultured human cells from two different tissues grown under controlled experimental conditions. The modal and average numbers of silver positive nucleolus organizers (NOs) per cell as well as the distribution of cells with different numbers of silver positive NO...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00293027
更新日期：1985-01-01 00:00:00
abstract：:A segregation analysis on 135 Duchenne families from Venetia (Italy) suggests that the proportion of sporadic cases might be less than expected. Support for this view is also given by an analysis of a pooled sample including 284 additional sibships from comparable studies published previously. Several hypotheses were ...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00291351
更新日期：1984-01-01 00:00:00
abstract：:High resolution cytogenetics, microsatellite marker analyses, and fluorescence in situ hybridization were used to define Xq deletions encompassing the fragile X gene, FMR1, detected in individuals from two unrelated families. In Family 1, a 19-year-old male had facial features consistent with fragile X syndrome; howev...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/s004390050501
更新日期：1997-08-01 00:00:00
abstract：:This paper describes two families in which four boys and two girls were affected with geroderma osteodysplastica. The major features of this syndrome include a droopy, jowly, prematurely aged appearance that has been likened by previous authors to the dwarfs in Walt Disney's 'Snow White.' Also, their skin lacks normal...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/BF00272192
更新日期：1978-02-16 00:00:00
abstract：:Catalase is an important antioxidant enzyme that detoxifies H2O2 into oxygen and water and thus limits the deleterious effects of reactive oxygen species (ROS). Because chronic exposure to excess ROS may contribute to vascular damage, we investigated whether genetic variation in catalase was associated with susceptibi...
journal_title：Human genetics
pub_type： 杂志文章
doi：10.1007/s004390100553
更新日期：2001-07-01 00:00:00
