Abstract:
:We previously reported the finding of phytosterolemia, xanthomatosis, and hyperapobetalipoproteinemia (hyperapoB) in five siblings in a large Amish pedigree ascertained through a 13-year-old boy who died suddenly from advanced coronary atherosclerosis. Here, we present further analyses of the plasma levels of the plant sterol, sitosterol, of low density (beta) lipoprotein (LDL) sterol, and of LDL B protein. Of 254 relatives and spouses of the proband, 90.5% were examined. A series of genetic models were explored using a pedigree analysis where parameters reflecting frequency, transmission, and penetrance of putative genotypes were examined simultaneously using a maximum likelihood approach. Segregation analysis of the sitosterol levels showed that the phenotype of sitosterolemia was controlled by a rare autosomal recessive gene. There was also significant familial correlation in plasma sitosterol levels that was attributed to a polygenic component under a mixed model but could also be due to shared environments such as diets. The recessive model was supported by our finding that the plasma sitosterol levels in the parents and in six children born to three of the five sitosterolemics were less than 1 mg/dl, well within the normal range. The phenotype of hyperapoB is based on an elevated level of LDL B protein in the presence of a normal LDL cholesterol level (low LDL sterol to LDL B ratio). For both LDL sterol and LDL B, a polygenic model showed a slightly greater improvement in ln likelihood than did the Mendelian single locus model when both were compared to a sporadic model. Similar results were obtained for sterol levels of high density (alpha) lipoprotein (HDL) sterol. When segregation analysis was performed using the ratio of LDL sterol to LDL B, the Mendelian single locus model gave a slightly better fit to the data than did the polygenic model. While the analyses presented here provided unequivocal evidence for the recessive phenotype of phytosterolemia, we also identified a possible single gene factor that could account for the major portion of the strong familial aggregation in the ratio of LDL sterol to LDL B, and to a lesser extent LDL B. However, there is clear evidence of familial aggregation for these traits in this pedigree beyond that due to Mendelian components.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Beaty TH,Kwiterovich PO Jr,Khoury MJ,White S,Bachorik PS,Smith HH,Teng B,Sniderman Asubject
Has Abstractpub_date
1986-04-01 00:00:00pages
492-504issue
4eissn
0002-9297issn
1537-6605journal_volume
38pub_type
杂志文章abstract::Ca2+ signaling is vital for various cellular processes including synaptic vesicle exocytosis, muscle contraction, regulation of secretion, gene transcription, and cellular proliferation. The endoplasmic reticulum (ER) is the largest intracellular Ca2+ store, and dysregulation of ER Ca2+ signaling and homeostasis contr...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.09.014
更新日期:2018-11-01 00:00:00
abstract::Approximately 5% of patients with neurofibromatosis type 1 (NF1) exhibit gross deletions that encompass the NF1 gene and its flanking regions. The breakpoints of the common 1.4-Mb (type 1) deletions are located within low-copy repeats (NF1-REPs) and cluster within a 3.4-kb hotspot of nonallelic homologous recombinatio...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/522089
更新日期:2007-12-01 00:00:00
abstract::Pedigrees used in the analysis of genetic or medical data are usually ascertained from sources subject to a variety of errors including misidentification of individuals, faults in historical documents or record linkage, nonpaternity, and unidentified adoption. Genetic markers can be used to verify putative family and ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
abstract::The power of structured exploratory data analysis (SEDA) to discriminate among major genic, polygenic, and nongenetic determination of phenotypes was investigated using computer simulation. Three classes of SEDA indices (the major gene index, the offspring between parents function, and the midparent-child correlation ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1984-01-01 00:00:00
abstract::The Million Veteran Program (MVP), initiated by the Department of Veterans Affairs (VA), aims to collect biosamples with consent from at least one million veterans. Presently, blood samples have been collected from over 800,000 enrolled participants. The size and diversity of the MVP cohort, as well as the availabilit...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2020.03.004
更新日期:2020-04-02 00:00:00
abstract::Both sequence variation and copy-number variation (CNV) of the genes encoding receptors for immunoglobulin G (Fcγ receptors) have been genetically and functionally associated with a number of autoimmune diseases. However, the molecular nature and evolutionary context of this variation is unknown. Here, we describe the...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.04.018
更新日期:2012-06-08 00:00:00
abstract::Urinary voiding dysfunction in childhood, manifesting as incontinence, dysuria, and urinary frequency, is a common condition. Urofacial syndrome (UFS) is a rare autosomal recessive disease characterized by facial grimacing when attempting to smile and failure of the urinary bladder to void completely despite a lack of...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2010.05.006
更新日期:2010-06-11 00:00:00
abstract::Electrophoretic properties of eight lysosomal hydrolases and 36 nonlysosomal enzymes were investigated in cultured fibroblasts from children with the inherited storage disease mucolipidosis II (ML II); fibroblasts from a child with a related disorder, mucolipidosis III (ML III); and two obligate heterozygous cell line...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1977-03-01 00:00:00
abstract::Escobar syndrome is a form of arthrogryposis multiplex congenita and features joint contractures, pterygia, and respiratory distress. Similar findings occur in newborns exposed to nicotinergic acetylcholine receptor (AChR) antibodies from myasthenic mothers. We performed linkage studies in families with Escobar syndro...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/506257
更新日期:2006-08-01 00:00:00
abstract::In a study of 908 males from Europe, northern Africa, and western Asia, the variation of four Y-linked dinucleotide microsatellites was analyzed within three "frames" that are defined by mutations that are nonrecurrent, or nearly so. The rapid generation and extinction of new dinucleotide length variants causes the ha...
journal_title:American journal of human genetics
pub_type: 杂志文章,多中心研究
doi:10.1086/301999
更新日期:1998-09-01 00:00:00
abstract::Myotubular myopathy is a severe congenital disease inherited as an X-linked trait (MTM1; McKusick 31040). It has been mapped to the long arm of chromosome X, to the Xq27-28 region. Significant linkage has subsequently been established for the linkage group comprised of DXS304, DXS15, DXS52, and F8C in several studies....
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1995-07-01 00:00:00
abstract::We have demonstrated that human lymphocytes can respond to the synthetic polypeptide GLPhe upon in vitro challenge by the antigen similar to that of (H,G)-A--L, (T,G)-A--L, (Phe,G)-A--L, and GAT. Family studies further support our postulation that responses to these synthetic polymers are under dual gene control. Thre...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1985-05-01 00:00:00
abstract::Serum and leukocyte hexosaminidase profiles (total activity and percent heat-labile activity levels) in obligate Sandhoff disease (SHD) heterozygotes differ from those of obligate Tay-Sachs disease (TSD) heterozygotes and noncarrier individuals. We have developed a procedure to identify, with 95% sensitivity, carriers...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1985-09-01 00:00:00
abstract::Allele and genotype frequencies for the highly polymorphic D1S80 locus were determined in a Finnish population sample by using PCR followed by high-resolution PAGE and silver staining, a procedure called the amplified-fragment-length polymorphism (Amp-FLP) technique. In 140 unrelated Finnish individuals 15 alleles and...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-04-01 00:00:00
abstract::Two of the three class I alcohol dehydrogenase (ADH) genes (ADH2 and ADH3) encode known functional variants that act on alcohol with different efficiencies. Variants at both these genes have been implicated in alcoholism in some populations because allele frequencies differ between alcoholics and controls. Specificall...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302317
更新日期:1999-04-01 00:00:00
abstract::While genetic causes are known for many syndromes involving developmental anomalies, a large number of individuals with overlapping phenotypes remain undiagnosed. Using exome-sequencing analysis and review of matchmaker databases, we have discovered four de novo missense variants predicted to affect the N-terminal reg...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.06.015
更新日期:2019-08-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1976-01-01 00:00:00
abstract::A rare germ-line polymorphism in codon 47 of the p53 gene replaces the wild-type proline (CCG) with a serine (TCG). Restriction analysis of 101 human samples revealed the frequency of the rare allele to be 0% (n = 69) in Caucasians and 4.7% (3/64, n = 32) among African-Americans. To investigate the consequence of this...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
abstract::Subcutaneous adipose tissue stores excess lipids and maintains energy balance. We performed expression quantitative trait locus (eQTL) analyses by using abdominal subcutaneous adipose tissue of 770 extensively phenotyped participants of the METSIM study. We identified cis-eQTLs for 12,400 genes at a 1% false-discovery...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2017.01.027
更新日期:2017-03-02 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::The heterogeneous nuclear ribonucleoprotein (HNRNP) genes code for a set of RNA-binding proteins that function primarily in the spliceosome C complex. Pathogenic variants in these genes can drive neurodegeneration, through a mechanism involving excessive stress-granule formation, or developmental defects, through mech...
journal_title:American journal of human genetics
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doi:10.1016/j.ajhg.2019.03.024
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/301922
更新日期:1998-07-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302799
更新日期:2000-03-01 00:00:00
abstract::Cerebello-oculo-renal syndromes (CORSs) and Joubert syndrome (JS) are clinically and genetically heterogeneous autosomal recessive syndromes that share a complex neuroradiological malformation resembling a molar tooth on brain axial images, a condition referred to as "molar tooth on imaging" (MTI) or the "molar tooth ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/378241
更新日期:2003-09-01 00:00:00
abstract::Interleukin-12 (IL12) is a cytokine that is secreted by activated phagocytes and dendritic cells and that induces interferon-gamma production by natural-killer and T lymphocytes. It consists of two subunits, p35 and p40, which are encoded by IL12A and IL12B, respectively. The first reported patient with a genetic cyto...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/338625
更新日期:2002-02-01 00:00:00
abstract::Osteogenesis imperfecta (OI) is a heritable disorder that ranges in severity from death in the perinatal period to an increased lifetime risk of fracture. Mutations in COL1A1 and COL1A2, which encode the chains of type I procollagen, result in dominant forms of OI, and mutations in several other genes result in recess...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.02.009
更新日期:2013-04-04 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/511312
更新日期:2007-02-01 00:00:00
abstract::Charcot-Marie-Tooth disease type 2D (CMT2D) and distal spinal muscular atrophy type V (dSMA-V) are axonal peripheral neuropathies inherited in an autosomal dominant fashion. Our previous genetic and physical mapping efforts localized the responsible gene(s) to a well-defined region on human chromosome 7p. Here, we rep...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/375039
更新日期:2003-05-01 00:00:00
abstract::Genome regions containing multiple copies of homologous genes, such as the immunoglobulin (Ig) heavy-chain constant-region (IGHC) locus, are often unstable and give rise to duplicated and deleted haplotypes. Analysis of such processes is fundamental to understanding the mechanisms of evolution of multigene families. I...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-04-01 00:00:00
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journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/375538
更新日期:2003-06-01 00:00:00