Abstract:
:Differential allelic expression has been shown to be common in mice, humans and maize, and variability in the expression of polymorphic alleles has been associated with human disease. Here, we describe the differential expression pattern of Paraoxonase-1, a gene involved in lipid metabolism and implicated in the formation of atherosclerotic lesions. We measured the expression of the murine Paraoxonase-1 gene (Pon1) in livers at different stages of embryonic development using F1 hybrid crosses and quantified the transcriptional level of both parental alleles. Using human foetal tissues, we analysed the expression of the human orthologue (PON1) and found monoallelic or preferential allelic expression in 6/7 and 4/4 samples from liver and pancreas, respectively. We observed that Pon1 does not show a parent-of-origin preference in its allelic expression, but has dramatic variations in allele-specific expression occurring throughout development. This study has important repercussions in the analysis of haplotypes at disease loci, since it implies that the expression of polymorphic alleles can be unequal and dynamic.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Parker-Katiraee L,Bousiaki E,Monk D,Moore GE,Nakabayashi K,Scherer SWdoi
10.1093/hmg/ddn222subject
Has Abstractpub_date
2008-11-01 00:00:00pages
3263-70issue
21eissn
0964-6906issn
1460-2083pii
ddn222journal_volume
17pub_type
杂志文章abstract::Epidermolytic hyperkeratosis (EHK), (bullous congenital ichthyosiform erythroderma), is an autosomal dominant human skin disorder. Recently, we and others have described mutations in keratins 1 and 10 (K1 and K10) in patients with this disease. Structure-function models predict that these mutations would impair normal...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.12.2147
更新日期:1993-12-01 00:00:00
abstract::The human genome is often portrayed as consisting of three sequence types, each distinguished by their mode of evolution. Purifying selection is estimated to act on 2.5-5.0% of the genome, whereas virtually all remaining sequence is considered to have evolved neutrally and to be devoid of functionality. The third mode...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/ddl182
更新日期:2006-10-15 00:00:00
abstract::Progressive myoclonus epilepsy of Lafora type (LD, MIM 254780) is a fatal autosomal recessive disorder characterized by the presence of progressive neurological deterioration, myoclonus, epilepsy and polyglucosan intracellular inclusion bodies, called Lafora bodies. Lafora bodies resemble glycogen with reduced branchi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddg340
更新日期:2003-12-01 00:00:00
abstract::Fourteen neurological diseases have been associated with the expansion of trinucleotide repeat regions. These diseases have been categorized into those that give rise to the translation of toxic polyglutamine proteins and those that are untranslated. Thus far, compelling evidence has not surfaced for the inclusion of ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.15.1531
更新日期:2001-07-15 00:00:00
abstract::The CCG rich sequence immediately 3' to the CAG repeat that is expanded in Huntington's disease (HD) has recently been shown to be polymorphic with at least 4 alleles differing by multiples of 3 bp being found in the normal population. We have studied the allele distribution in 180 HD families resident in Scotland and...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/3.1.173
更新日期:1994-01-01 00:00:00
abstract::Lethal white foal syndrome (LWFS) is a congenital anomaly of horses characterized by a white coat colour and aganglionosis of the bowel, which is similar to Hirschsprung disease (HSCR). We decided to investigate possible mutations of the endothelin-B receptor gene ( EDNRB ) in LWFS as recent studies in mutant rodents ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.6.1047
更新日期:1998-06-01 00:00:00
abstract::What would define real progress in the field of deafness research in fundamental and medical terms? In fundamental terms, progress would be measured by an improvement in our knowledge of the development and physiology of the ear. In medical terms, progress would lead to the division of the broad category of hearing de...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
doi:10.1093/hmg/7.10.1589
更新日期:1998-01-01 00:00:00
abstract::Newborn screening (NBS) for medium-chain acyl-CoA dehydrogenase deficiency (MCADD) revealed a higher birth prevalence and genotypic variability than previously estimated, including numerous novel missense mutations in the ACADM gene. On average, these mutations are associated with milder biochemical phenotypes raising...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp079
更新日期:2009-05-01 00:00:00
abstract::The ε4 allele of the APOE gene encoding apolipoprotein E (apoE) is a strong genetic risk factor for aging-related cognitive decline as well as late-onset Alzheimer's disease (AD) compared to the common ε3 allele. In the central nervous system, apoE is produced primarily by astrocytes and functions in transporting lipi...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx155
更新日期:2017-07-15 00:00:00
abstract::The gene B lymphocyte kinase (BLK) is associated with rheumatoid arthritis, systemic lupus erythematosus and several other autoimmune disorders. The disease risk haplotype is known to be associated with reduced expression of BLK mRNA transcript in human B cell lines; however, little is known about cis-regulation of BL...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds220
更新日期:2012-09-01 00:00:00
abstract::Presenilins 1 and 2 (PS1/2), causative molecules for familial Alzheimer's disease (FAD), are multipass transmembrane proteins localized predominantly in the endoplasmic reticulum (ER) and Golgi apparatus. Heteromeric protein complexes containing PS1/2 are thought to participate in several functions, including intramem...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi195
更新日期:2005-07-01 00:00:00
abstract::Duchenne muscular dystrophy (DMD) is a lethal X-linked recessive disorder with a high spontaneous mutation rate and no effective treatment, hence development of genetic based therapies is an important goal. We report that expression of a recombinant human minidystrophin cDNA, compatible with current viral vectors, can...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.8.1245
更新日期:1995-08-01 00:00:00
abstract::Chediak-Higashi syndrome is an autosomal recessive, immune deficiency disorder of human (CHS) and mouse (beige, bg) that is characterized by abnormal intracellular protein transport to, and from, the lysosome. Recent reports have described the identification of homologous genes that are mutated in human CHS and bg mic...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/6.7.1091
更新日期:1997-07-01 00:00:00
abstract::Deletions within the neurexin 1 gene (NRXN1; 2p16.3) are associated with autism and have also been reported in two families with schizophrenia. We examined NRXN1, and the closely related NRXN2 and NRXN3 genes, for copy number variants (CNVs) in 2977 schizophrenia patients and 33 746 controls from seven European popula...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddn351
更新日期:2009-03-01 00:00:00
abstract::While constructing a cDNA library of human embryos, we have isolated a clone homologous to jumonji, a mouse gene required for neural tube formation. We have determined the complete coding sequence of the human homologue (JMJ) and deduced the amino acid sequence of the putative protein. We show here that human and mous...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.10.1637
更新日期:1996-10-01 00:00:00
abstract::The infantile neuronal ceroid lipofuscinosis (INCL), a rare (one in 100 000 births) but one of the most lethal inherited neurodegenerative storage disorders of childhood, is caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 cleaves thioester linkages in s-acylated (palmitoylate...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl078
更新日期:2006-05-15 00:00:00
abstract::We performed a molecular study with 21 microsatellites on a sample of 82 trisomy 13 conceptuses, the largest number of cases studied to date. The parental origin was determined in every case and in 89% the extra chromosome 13 was of maternal origin with an almost equal number of maternal MI and MII errors. The latter ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm148
更新日期:2007-08-15 00:00:00
abstract::Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in either of two genes, TSC1 or TSC2, resulting in the constitutive activation of the mammalian target of rapamycin complex 1 (mTORC1). mTOR inhibitors are now considered the treatment of choice for TSC disease. A major path...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx214
更新日期:2017-09-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a progressive motor neurodegeneration resulting in paralysis and death from respiratory failure within 3-5 years. About 20% of familial cases are associated with mutations in the gene for copper/zinc superoxide dismutase ( SOD1 ), which catalyses the dismutation of the superoxide...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.13.2045
更新日期:1998-12-01 00:00:00
abstract::Genetic and environmental influences are thought to interact in their contribution to the etiology of major neuropsychiatric disorders. One of the best replicated findings obtained in genome-wide association studies are genetic variants in the CACNA1C gene. Here, we used our constitutive heterozygous Cacna1c rat model...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz235
更新日期:2019-12-15 00:00:00
abstract::A recurrent t(9;22) (q22;q12) chromosome translocation has been described in extraskeletal myxoid chondrosarcoma (EMC). Fluorescent in situ hybridization experiments performed on one EMC tumour indicated that the chromosome 22 breakpoint occurred in the EWS gene. Northern blot analysis revealed an aberrant EWS transcr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.12.2219
更新日期:1995-12-01 00:00:00
abstract::Both genetic and environmental factors contribute to the development of intellectual disability (ID). Previously, we identified a promoter variant (-113C>A) in PLP2 (proteolipid protein 2) that results in an ∼4-fold reduction of transcript and protein and is overly represented in males with X-linked ID (XLID). The fun...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv422
更新日期:2015-12-20 00:00:00
abstract::Failures in neurotrophic support and signalling play key roles in Alzheimer's disease (AD) pathogenesis. We previously demonstrated that downregulation of the neurotrophin effector Kinase D interacting substrate (Kidins220) by excitotoxicity and cerebral ischaemia contributed to neuronal death. This downregulation, tr...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds446
更新日期:2013-02-01 00:00:00
abstract::Carnitine palmitoyltransferase (CPT) II deficiency is the most common inherited disorder of lipid metabolism affecting skeletal muscle. To facilitate the identification of disease-causing mutations in the CPT II gene (CPT1), we have established the genomic organization of this gene. CPT1 spans approximately 20 kb of 1...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.1.19
更新日期:1995-01-01 00:00:00
abstract::The first 17 amino acids of Huntington's disease (HD) protein, huntingtin, comprise an amphipathic alpha-helical domain that can target huntingtin to the endoplasmic reticulum (ER). N17 is phosphorylated at two serines, shown to be important for disease development in genetic mouse models, and shown to be modified by ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds554
更新日期:2013-04-01 00:00:00
abstract::The genomic instability of persons with Bloom's syndrome (BS) features particularly an increased number of sister-chromatid exchanges (SCEs). The primary cause of the genomic instability is mutation at BLM, which encodes a DNA helicase of the RecQ family. BLM interacts with Topoisomerase IIIalpha (Topo IIIalpha), and ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.12.1287
更新日期:2001-06-01 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are the two common neurodegenerative diseases that have been associated with the GGGGCC·GGCCCC repeat RNA expansion in a noncoding region of C9orf72. It has been previously reported that unconventional repeat-associated non-ATG (RAN) translation of ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddv005
更新日期:2015-05-01 00:00:00
abstract::Understanding the biological functions of tau variants can illuminate differential etiologies of Alzheimer's disease (AD) and primary tauopathies. Though the end-stage neuropathological attributes of AD and primary tauopathies are similar, the etiology and behavioral outcomes of these diseases follow unique and diverg...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddz151
更新日期:2019-10-01 00:00:00
abstract::The intraflagellar transport (IFT) machinery containing the IFT-A and IFT-B complexes mediates ciliary protein trafficking. Mutations in the genes encoding the six subunits of the IFT-A complex (IFT43, IFT121, IFT122, IFT139, IFT140, and IFT144) are known to cause skeletal ciliopathies, including cranioectodermal dysp...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddx421
更新日期:2018-02-01 00:00:00
abstract::The FMR1 gene, associated with fragile X syndrome, has recently been cloned and the sequence of partial cDNA clones is known. We have determined additional cDNA sequences both at the 5' and 3' end. We have characterized the expressed gene by means of RT-PCR in various tissues and have found that alternative splicing t...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/2.4.399
更新日期:1993-04-01 00:00:00