Abstract：
:Recombination rates vary both across the genome and between different species, but little information is available about the temporal and physical scales over which such rates change. To shed light on these questions, we performed a high-resolution analysis of a genomic region within the beta-globin gene cluster that is known to experience elevated recombination rates in humans. For this purpose, we developed new linkage disequilibrium-based methods that thoroughly search for subsets of the data with unusually high or unusually low estimated values of the population-recombination parameter (4Nr, where N is the effective population size and r is the crossover rate between adjacent base pairs). By resequencing a 15-kb segment in a human population sample, we were able to narrow the recombinational hotspot to a segment <2 kb in length that coincides with the beta-globin replication origin. In addition, we analyzed the orthologous region in samples of rhesus macaques and common chimpanzees. Whereas the analysis of the chimpanzee data is complicated by the sample structure, the macaque data imply that this region may not be a hotspot in that species. These results suggest a time scale for the evolution of hotspots in primates. Furthermore, they allow us to propose diverged sequence elements that may contribute to the differences in the recombinational landscape in the two species.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Wall JD,Frisse LA,Hudson RR,Di Rienzo Adoi
10.1086/380311subject
Has Abstractpub_date
2003-12-01 00:00:00pages
1330-40issue
6eissn
0002-9297issn
1537-6605pii
S0002-9297(07)63985-8journal_volume
73pub_type
杂志文章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 ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-07-01 00:00:00
abstract：:Cone-rod dystrophy (CRD) and retinitis pigmentosa (RP) are clinically and genetically overlapping heterogeneous retinal dystrophies. By using homozygosity mapping in an individual with autosomal-recessive (ar) RP from a consanguineous family, we identified three sizeable homozygous regions, together encompassing 46 Mb...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2011.11.015
更新日期：2012-01-13 00:00:00
abstract：:A proband, clinically thought to have trisomy 10p, was found to have an inverted duplication of 10p [46, XY, inv dup(10)(qter----p15.3::p15.3----p 11.1:)]. The phenotypic findings and cytogenetic observations were supported by relevant biochemical studies. The activity of phosphofructokinase (platelet-type; PFKP), pre...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1984-07-01 00:00:00
abstract：:Age at onset of motor symptoms was collected on 611 persons affected with Huntington disease (HD) among 3,201 persons "at risk" in 108 kindreds. Life-table estimates correcting for truncated intervals of observation (censoring) produced a median age at onset 5 years older than the observed mean. Risk estimates of HD o...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-11-01 00:00:00
abstract：:Although balanced translocations are among the most common human chromosomal aberrations, the constitutional t(11;22)(q23;q11) is the only known recurrent non-Robertsonian translocation. Evidence indicates that de novo formation of the t(11;22) occurs during meiosis. To test the hypothesis that spatial proximity of ch...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/507652
更新日期：2006-09-01 00:00:00
abstract：:Lymphedema is the clinical manifestation of defects in lymphatic structure or function. Mutations identified in genes regulating lymphatic development result in inherited lymphedema. No mutations have yet been identified in genes mediating lymphatic function that result in inherited lymphedema. Survey microarray studi...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.04.010
更新日期：2010-06-11 00:00:00
abstract：:Allele-specific replication differences have been observed in imprinted chromosomal regions. We have exploited this characteristic of an imprinted region by using FISH at D15S9 and SNRPN (small nuclear ribonucleo protein N) on interphase nuclei to distinguish between Angelman and Prader-Willi syndrome patient samples ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-08-01 00:00:00
abstract：:Renal stone formation is a common multifactorial disorder, of unknown etiology, with an established genetic contribution. Lifetime risk for nephrolithiasis is approximately 10% in Western populations, and uric acid stones account for 5%-10% of all stones, depending on climatic, dietary, and ethnic differences. We stud...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/320105
更新日期：2001-05-01 00:00:00
abstract：:Deletions of the long arm of chromosome 18 occur in approximately 1 in 10,000 live births. Congenital aural atresia (CAA), or narrow external auditory canals, occurs in approximately 66% of all patients who have a terminal deletion 18q. The present report describes a series of 20 patients with CAA, of whom 18 had micr...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/375695
更新日期：2003-06-01 00:00:00
abstract：:Genetic defects affecting motility of cilia and flagella cause chronic destructive airway disease, randomization of left-right body asymmetry, and, frequently, male infertility in primary ciliary dyskinesia (PCD). The most frequent defects involve outer and inner dynein arms (ODAs and IDAs) that are large multiprotein...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2009.10.018
更新日期：2009-12-01 00:00:00
abstract：:We report the transmission of HLA haplotypes and Gm allotypes in 97 members of a single kindred containing 257 individuals, 45 of whom were determined by clinical examination, autopsy, or historical data to have had Alzheimer disease (AD). Extensive inbreeding suggests that more than one gene may contribute to suscept...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
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 ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2010.06.005
更新日期：2010-07-09 00:00:00
abstract：:Hereditary fructose intolerance (HFI) is an inborn error of metabolism, inherited as an autosomal recessive disorder and caused by a decrease in the activity of fructose-1-phosphate aldolase (aldolase B) in affected individuals. Investigation of the molecular basis of HFI is reported here by the identification of two ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-06-01 00:00:00
abstract：:The polymerase chain reaction (PCR) makes it possible to rapidly generate a very large number of copies of a specific region of DNA. Application of PCR to individual human sperm cells permits the typing of a large number of independent male meiotic events. If the donor male is heterozygous at three loci, sperm typing ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-07-01 00:00:00
abstract：:Supernumerary marker chromosomes (SMCs) of chromosome 15, designated "SMC(15)s," are the most common SMC in humans, accounting for as much as 60% of all those observed. We report the characterization of 46 large SMC(15)s, using both fluorescence in situ hybridization and polymerase chain reaction analysis within and d...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/379155
更新日期：2003-11-01 00:00:00
abstract：:A current approach to mapping complex-disease-susceptibility loci in genome-wide association (GWA) studies involves leveraging the information in a reference database of dense genotype data. By modeling the patterns of linkage disequilibrium in a reference panel, genotypes not directly measured in the study samples ca...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2009.01.013
更新日期：2009-02-01 00:00:00
abstract：:Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mut...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-07-01 00:00:00
abstract：:Many ion channel genes have been associated with human genetic pain disorders. Here we report two large Chinese families with autosomal-dominant episodic pain. We performed a genome-wide linkage scan with microsatellite markers after excluding mutations in three known genes (SCN9A, SCN10A, and TRPA1) that cause simila...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2013.09.016
更新日期：2013-11-07 00:00:00
abstract：:Leber congenital amaurosis (LCA) is a neurodegenerative disease of photoreceptor cells that causes blindness within the first year of life. It occasionally occurs in syndromic metabolic diseases and plurisystemic ciliopathies. Using exome sequencing in a multiplex family and three simplex case subjects with an atypica...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2017.10.010
更新日期：2017-12-07 00:00:00
abstract：:Two hundred subjects with insulin-dependent (type I) diabetes mellitus (IDDM) were typed for HLA-B, HLA-DR, and properdin factor B (Bf). HLA and Bf antigen and haplotype frequencies in subjects were compared with control frequencies derived from the 8th HLA Workshop. Frequencies of extended haplotypes (defined by B-Bf...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1984-09-01 00:00:00
abstract：:Spinal muscular atrophy (SMA) is a clinically and genetically heterogeneous disease characterized by the degeneration of lower motor neurons. The most frequent form is linked to mutations in SMN1. Childhood SMA associated with progressive myoclonic epilepsy (SMA-PME) has been reported as a rare autosomal-recessive con...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.05.001
更新日期：2012-07-13 00:00:00
abstract：:The hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and highly elevated levels of serum IgE. HIES is now recognized as a multisystem disorder, with nonimmunologic abnormalities of the dentition, bones, and connective tissue. HIES can be transmitted as ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302547
更新日期：1999-09-01 00:00:00
abstract：:We present a systematic review of pleiotropy among SNPs and genes reported to show genome-wide association with common complex diseases and traits. We find abundant evidence of pleiotropy; 233 (16.9%) genes and 77 (4.6%) SNPs show pleiotropic effects. SNP pleiotropic status was associated with gene location (p = 0.024...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：10.1016/j.ajhg.2011.10.004
更新日期：2011-11-11 00:00:00
abstract：:Estimation of recombination fractions and interference coefficients is of importance in multilocus linkage analysis. With the development of molecular genetic technologies such as RFLP, multilocus data are readily available to researchers. Several methods have been developed to analyze such data, and each performs wel...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-08-01 00:00:00
abstract：:We offered cystic fibrosis (CF) carrier testing to reproductive-age enrollees in an HMO, in order to determine factors associated with test utilization in a primarily nonpregnant population. Male and female enrollees either were mailed an invitation to have the test after attending an educational session (N = 2,713) o...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-10-01 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：:Keratitis-ichthyosis-deafness syndrome (KID) is a rare ectodermal dysplasia characterized by vascularizing keratitis, profound sensorineural hearing loss (SNHL), and progressive erythrokeratoderma, a clinical triad that indicates a failure in development and differentiation of multiple stratifying epithelia. Here, we ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/339986
更新日期：2002-05-01 00:00:00
abstract：:Steroid-resistant nephrotic syndrome (SRNS) is characterized by high-range proteinuria and most often focal and segmental glomerulosclerosis (FSGS). Identification of mutations in genes causing SRNS has improved our understanding of disease mechanisms and highlighted defects in the podocyte, a highly specialized glome...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2018.12.016
更新日期：2019-02-07 00:00:00
abstract：:Two familial and seven sporadic patients with neurofibromatosis 1-who showed dysmorphism, learning disabilities/mental retardation, and additional signs and carried deletions of the NF1 gene-were investigated by use of a two-step FISH approach to characterize the deletions. With FISH of YAC clones belonging to a 7-Mb ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302709
更新日期：2000-01-01 00:00:00
abstract：:In humans, deviations from a 1:1 male:female ratio have been identified in both chromosomally normal and trisomic live births: among normal newborns there is a slight excess of males, among trisomy 18 live borns a large excess of females, and among trisomy 21 live borns an excess of males. These differences could aris...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-11-01 00:00:00
