Abstract:
:Lactase is the intestinal enzyme responsible for digestion of the milk sugar lactose. Lactase gene expression declines dramatically upon weaning in mammals and during early childhood in humans (lactase nonpersistence). In various ethnic groups, however, lactase persists in high levels throughout adulthood (lactase persistence). Genetic association studies have identified that lactase persistence in northern Europeans is strongly associated with a single nucleotide polymorphism (SNP) located 14 kb upstream of the lactase gene: -13910*C/T. To determine whether the -13910*T SNP can function in vivo to mediate lactase persistence, we generated transgenic mice harboring human DNA fragments with the -13910*T SNP or the ancestral -13910*C SNP cloned upstream of a 2-kb rat lactase gene promoter in a luciferase reporter construct. We previously reported that the 2-kb rat lactase promoter directs a post-weaning decline of luciferase transgene expression similar to that of the endogenous lactase gene. In the present study, the post-weaning decline directed by the rat lactase promoter is impeded by addition of the -13910*T SNP human DNA fragment, but not by addition of the -13910*C ancestral SNP fragment. Persistence of transgene expression associated with the -13910*T SNP represents the first in vivo data in support of a functional role for the -13910*T SNP in mediating the human lactase persistence phenotype.
journal_name
Hum Genetjournal_title
Human geneticsauthors
Fang L,Ahn JK,Wodziak D,Sibley Edoi
10.1007/s00439-012-1140-zsubject
Has Abstractpub_date
2012-07-01 00:00:00pages
1153-9issue
7eissn
0340-6717issn
1432-1203journal_volume
131pub_type
杂志文章相关文献
HUMAN GENETICS文献大全abstract::The aim of this study was to estimate the risk of viable unbalanced offspring for a parental carrier of reciprocal translocation. On a large computerized database of reciprocal translocations we used logistic regression to model this risk. The status of the progeny is the outcome variable. Explanatory covariates are c...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00420946
更新日期:1993-12-01 00:00:00
abstract::Eukaryotic genomes contain 5-methylcytosine (5mC) as a rare base.5mC arises by postsynthetic modification of cytosine and occurs, at least in animals, predominantly in the dinucleotide CpG. The base is not distributed randomly in these genomes but conforms to a pattern. This pattern varies between taxa but appears to ...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/BF00292363
更新日期:1983-01-01 00:00:00
abstract::Clinical exome sequencing (CES) has become an increasingly popular diagnostic tool in patients with heterogeneous genetic disorders, especially in those with neurocognitive phenotypes. Utility of CES in consanguineous populations has not yet been determined on a large scale. A clinical cohort of 149 probands from Qata...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-015-1575-0
更新日期:2015-09-01 00:00:00
abstract::Deficient debrisoquine/sparteine type oxidation is inherited as an autosomal recessive trait. Of all Caucasians, 5-10% are poor metabolisers, due to the absence of cytochrome P4502D6. Extensive metabolisers (EMs) exhibit highly variable metabolic activity. We investigated the relationship between CYP2D6 activity and g...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF01247337
更新日期:1993-10-01 00:00:00
abstract::A single base substitution is responsible for the PI-Z mutation in alpha-1-antitrypsin (AAT) deficiency. The Z mutation, which is in exon V of the AAT gene, was analysed directly using a primer designed with a single base substitution in the DNA sequence. During the polymerase chain reaction with this primer, a restri...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00201739
更新日期:1991-10-01 00:00:00
abstract::Admixture mapping is a potentially powerful tool for mapping complex genetic diseases. For application of this method, admixed individuals must have genomes composed of large segments derived intact from each founding population. Such segments are thought to be present in African Americans (AA) and should be demonstra...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-003-0961-1
更新日期:2003-08-01 00:00:00
abstract::During a survey of the mutations of the low density lipoprotein receptor (LDL-R) gene in Italian patients with familial hypercholesterolemia (FH), we identified a novel point mutation, that creates a new EcoRI site at the 5' end of exon 7, in a heterozygous FH subject (FH-100). The sequence of a cDNA fragment encompas...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00202819
更新日期:1994-05-01 00:00:00
abstract::Genetics-associated asthenoteratozoospermia is often seen in patients with multiple morphological abnormalities of the sperm flagella (MMAF). Although 24 causative genes have been identified, these explain only approximately half of patients with MMAF. Since sperm flagella and motile cilia (especially respiratory cili...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-020-02241-4
更新日期:2021-01-03 00:00:00
abstract::In human females, both X chromosomes are equivalent in size and genetic content, and pairing and recombination can theoretically occur anywhere along their entire length. In human males, however, only small regions of sequence identity exist between the sex chromosomes. Recombination and genetic exchange is restricted...
journal_title:Human genetics
pub_type: 杂志文章,评审
doi:10.1007/BF01247327
更新日期:1993-10-01 00:00:00
abstract::Human height is a complex trait regulated by multiple genetic and environmental factors. CYP19 (cytochrome P450 19) encodes aromatase, which catalyses the rate-limiting step in the conversion of androgens to estrogens. Deleterious mutations in CYP19 can result in estrogen deficiency that will influence adult height to...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-006-0199-9
更新日期:2006-08-01 00:00:00
abstract::Most individuals with osteogenesis imperfecta (OI) are heterozygous for dominant mutations in one of the genes that encode the chains of type I collagen. Each of the more than 30 mutations characterized to date has been unique to the affected member(s) of the family. We have determined that two individuals with a prog...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF01213088
更新日期:1991-05-01 00:00:00
abstract::Case-control genetic association studies in admixed populations are known to be susceptible to genetic confounding due to population stratification. The transmission/disequilibrium test (TDT) approach can avoid this problem. However, the TDT is expensive and impractical for late-onset diseases. Case-control study desi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-005-0080-2
更新日期:2006-01-01 00:00:00
abstract::Angelman syndrome is a neuro-developmental disorder caused by genetic abnormalities affecting the maternal gene expression in the chromosome region 15q11-q13. In a study group of 45 Finnish Angelman patients, a recurrence of a del(15)(q11q13) was detected in one family. The mother's chromosomes 15 were structurally no...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390000336
更新日期:2000-07-01 00:00:00
abstract::A sample of South African Negroids (n = 791) was scored for each individual's Bf and GLO phenotype. (The genes for the Bf and GLO olymorphisms are included in a known cluster of linked genes on chromosome 6.) Following a x2-test the respective two series of alleles were found to be disturbed at random, i.e., there was...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00527407
更新日期:1977-09-22 00:00:00
abstract::Extensive studies have been conducted on the analysis of genome function, especially on the expression quantitative trait loci (eQTL). These studies offered promising results for characterization of the functional sequencing variation and understanding of the basic processes of gene regulation. Parent of origin effect...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-020-02162-2
更新日期:2020-08-01 00:00:00
abstract::Reverse transcription-polymerase chain reaction (RT-PCR)-based analyses of the adenomatous polyposis coli (APC) gene encompassing exons 1-15 revealed a complex pattern of products that were due to alternative splicing of exons 9, 10A and 14. The multiplicity of polypeptide chains obtained from T7-promoter-directed in ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050254
更新日期:1996-11-01 00:00:00
abstract::The possibility of using TaqI restriction fragment length polymorphism (RFLP) analysis of the HLA-B locus and the HLA-DR-DQ subregions, flanking the 21-hydroxylase genes, for predicting disease in siblings of children with 21-hydroxylase deficiency was analyzed in 12 nuclear families with at least one affected child a...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00194218
更新日期:1990-10-01 00:00:00
abstract::X-linked congenital adrenal hypoplasia (AHC) is a developmental disorder of the human adrenal gland that results in profound hormonal deficiencies, which are lethal if untreated. Hypogonadotropic hypogonadism (HHG) is frequently associated with this disorder. The gene (DAX-1) responsible for the disease has recently b...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050316
更新日期:1997-01-01 00:00:00
abstract::We have observed a T-->C mutation at position +96 of the untranslated region 3' to the terminating codon of the beta-globin gene in members of two Czech families and one black family. Data from initial studies suggested that this change was the cause of a beta-thalassemia, but continued analyses have provided convinci...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00218918
更新日期:1994-01-01 00:00:00
abstract::Three cases of partial trisomy for the distal segment of chromosome 13 are reported. Common clinical features included normal birth weight, postnatal asphyxia, convulsions, severe psychomotor retardation, normal growth, and a distinct pattern of dysmorphias consisting of trigonocephalic head with prominent metopic sut...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00569970
更新日期:1976-04-15 00:00:00
abstract::We have used Y-specific and Y-derived DNA probes for in situ hybridization and Southern blotting analysis to characterize a Y;15 translocation showing normal Mendelian inheritance in a family. Cytogenetically there appeared to be an unbalanced translocation of Yqh to 15p; this translocation may be considered as a prot...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291705
更新日期:1988-05-01 00:00:00
abstract::Neural tube defect disorders are developmental diseases that originate from an incomplete closure of the neural tube during embryogenesis. Despite high prevalence-1 out of 3000 live births-their etiology is not yet established and both environmental and genetic factors have been proposed, with a heritability rate of a...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-019-01993-y
更新日期:2019-04-01 00:00:00
abstract::Developmental and epileptic encephalopathies (DEEs) are genetically heterogenous conditions, often characterized by early onset, EEG interictal epileptiform abnormalities, polymorphous and drug-resistant seizures, and neurodevelopmental impairments. In this study, we investigated the genetic defects in two siblings wh...
journal_title:Human genetics
pub_type: 临床试验,杂志文章
doi:10.1007/s00439-019-01972-3
更新日期:2019-02-01 00:00:00
abstract::The length of 44 silver-stained human autosomal pachytene complements was shown to vary from about 300 micrometer to at least 535 micrometer. The lengths of the individual 22 autosomal chromosomes of eight complements representing this interval was measured and the relative lengths calculated. For most of the chromoso...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00293056
更新日期:1981-01-01 00:00:00
abstract::Acute intermittent porphyria (AIP) is a low-penetrant autosomal dominant disorder caused by mutations in the hydroxymethylbilane synthase (HMBS) gene. Direct detection of mutations is becoming the method of choice for the accurate identification of asymptomatic affected individuals within AIP families so that they can...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050995
更新日期:1999-06-01 00:00:00
abstract::We identified two informative polymorphisms in the transcribed 3' untranslated region of the tumor necrosis factor receptor 2 (TNFR2) gene using the polymerase chain reaction (PCR) with the single-strand conformation polymorphism (SSCP) technique. These polymorphisms demonstrated Mendelian inheritance and were useful ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00201604
更新日期:1994-10-01 00:00:00
abstract::Although several studies have demonstrated familial aggregation of nonsyndromic cleft palate (CP), the mode of inheritance still remains uncertain. We report the results of complex segregation analysis performed in families of 357 consecutive newborns affected with nonsyndromic CP (i.e., CP not a component feature of ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050491
更新日期:1997-08-01 00:00:00
abstract::Familial long QT syndrome (LQTS) is characterized by prolonged ventricular repolarization. Clinical symptoms include recurrent syncopal attacks, and sudden death may occur as a result of ventricular tachyarrhythmias. Three genes responsible for this syndrome (KVLQT1, HERG, and SCN5A) have been identified so far, and m...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050717
更新日期:1998-04-01 00:00:00
abstract::The pediatric eye-tumor retinoblastoma is widely held as a paradigm of human cancer genetics and has been a model system for both the two-hit hypothesis of dominantly inherited cancer as well as for the concept of tumor-specific loss of constitutional heterozygosity to achieve expression of the tumorigenic phenotype. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050551
更新日期:1997-10-01 00:00:00
abstract::Myotonic dystrophy (DM) is a dominantly inherited neuromuscular disorder characterised by muscle weakness and wasting. There are two forms of DM; both of which are caused by the expansion of repeated DNA sequences. DM1 is associated with a CTG repeat located in the 3' untranslated region of a gene, DMPK and DM2 with a...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-006-0228-8
更新日期:2006-11-01 00:00:00