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1.
Expressed sequence tags (ESTs) in the human chromosome 7q21-q31 region were recently used to screen for allelic expression
bias in monochromosomal hybrids retaining a paternal or maternal human chromosome 7. Six candidate imprinted genes were identified.
In this study, we investigated parent-of-origin-specific expression profiles of their mouse homologues in the proximal region
of chromosome 6. An imprinting analysis, using F1 mice from reciprocal crosses between the B6 and JF strains, demonstrated
that the mouse calcitonin receptor gene (Calcr) was expressed preferentially from the maternal allele in brain, whereas no allelic bias was detected in other tissues. Our
results indicate that Calcr is imprinted in a tissue-specific manner, with a predominant expression from the maternal allele in the brain.
Electronic Publication 相似文献
2.
Identification of an imprinted gene, Meg3/Gtl2 and its human homologue MEG3, first mapped on mouse distal chromosome 12 and human chromosome 14q 总被引:7,自引:0,他引:7
Miyoshi N Wagatsuma H Wakana S Shiroishi T Nomura M Aisaka K Kohda T Surani MA Kaneko-Ishino T Ishino F 《Genes to cells : devoted to molecular & cellular mechanisms》2000,5(3):211-220
BACKGROUND: The paternal duplication of mouse distal chromosome 12 leads to late embryonal/neonatal lethality and growth promotion, whereas maternal duplication leads to late embryonal lethality and growth retardation. Human paternal or maternal uniparental disomies of chromosome 14q that are syntenic to mouse distal chromosome 12 have also been reported to show some imprinting effects on growth, mental activity and musculoskeletal morphology. For the isolation of imprinted genes in this region, a systematic screen of maternally expressed genes (Megs) was carried out by our subtraction-hybridization method using androgenetic and normally fertilized embryos. RESULTS: We have isolated seven candidate clones of the mouse Meg gene. Among them, we identified a novel maternally expressed imprinted gene, Meg3, on mouse distal chromosome 12 and showed that it was identical to the Gtl2 gene. We also found that the human homologue MEG3 on chromosome 14q was also monoallelically expressed. CONCLUSIONS: This is the first identification of the imprinting gene, both on mouse distal chromosome 12 and on human chromosome 14q, respectively. Because there are no obvious open reading frames in either the mouse Meg3/Gtl2 or human MEG3, the function of these genes remains unclear. However, this result will provide a good basis for the further investigation of several important imprinted genes in this chromosomal region. 相似文献
3.
The necdin gene is deleted in Prader-Willi syndrome and is imprinted in human and mouse 总被引:9,自引:5,他引:9
Human chromosome 15q11-q13 contains genes that are imprinted and expressed
from only one parental allele. Prader-Willi syndrome (PWS) is due to the
loss of expression of one or more paternally expressed genes on proximal
human chromosome 15q, most often by deletion or maternal uniparental
disomy. Several candidate genes and a putative imprinting centre have been
identified in the deletion region. We report that the human necdin-encoding
gene (NDN) is within the centromeric portion of the PWS deletion region,
between the two imprinted genes ZNF127 and SNRPN. Murine necdin is a
nuclear protein expressed exclusively in differentiated neurons in the
brain. Necdin is postulated to govern the permanent arrest of cell growth
of post-mitotic neurons during murine nervous system development. We have
localized the mouse locus Ndn encoding necdin to chromosome 7 in a region
of conserved synteny with human chromosome 15q11-q13, by genetic mapping in
an interspecific backcross panel. Furthermore, we demonstrate that
expression of Ndn is limited to the paternal allele in RNA from newborn
mouse brain. Expression of NDN is detected in many human tissues, with
highest levels of expression in brain and placenta. NDN is expressed
exclusively from the paternally inherited allele in human fibroblasts. Loss
of necdin gene expression may contribute to the disorder of brain
development in individuals with PWS.
相似文献
4.
Amplified region (amplicon) around MLL gene is closely linked to the 11q23.3 commonly deleted region of neuroblastoma, which includes cancer-associated genes such as PHLDB1 (LL5A), BCL9L, FOXN5 (FOXR1), CBL, MFRP, and PVRL1 (Nectin) genes. FOXN6 (FOXR2) gene at human chromosome Xp11.21 is generated due to retrotransposition of ancestral Foxn5 gene during evolution. FOXN5 and FOXN6 orthologs share the common domain structure consisting of FN56 and Forhead-box (FOX) domains. Here, we identified and characterized mouse Foxn5 gene by using bioinformatics. Mouse Foxn5, consisting of six exons, was located within mouse genome sequences AC122428.4 and AC125129.5. Foxn5 locus at mouse chromosome 9B was synthenic to rat chromosome 8q22 and human chromosome 11q23.3. Mouse Foxn5 (180 aa) was C-terminally truncated compared with rat Foxn5 and human FOXN5. Mouse 'Foxn5' protein without FOX domain was generated due to a frame shift introduced by germ-line one-base deletion within exon 3. Mouse Foxn5 mRNA was expressed in embryonic germ cells and fertilized eggs. Germ-line mutation of Foxn5 gene in the mouse lineage might lead to divergent scenario of early embryogenesis between mouse and rat through the deregulation of Foxn5 target genes in mouse early embryos, and explain the difficulty in manipulation of rat embryonic stem (ES) cells based on the mouse equivalent system. This is the first report on identification and characterization of mouse Foxn5 gene as well as on species specific germ-line mutation of the Fox family gene. 相似文献
5.
Johnstone KA DuBose AJ Futtner CR Elmore MD Brannan CI Resnick JL 《Human molecular genetics》2006,15(3):393-404
Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are caused by the loss of imprinted gene expression from chromosome 15q11-q13. Imprinted gene expression in the region is regulated by a bipartite imprinting centre (IC), comprising the PWS-IC and the AS-IC. The PWS-IC is a positive regulatory element required for bidirectional activation of a number of paternally expressed genes. The function of the AS-IC appears to be to suppress PWS-IC function on the maternal chromosome through a methylation imprint acquired during female gametogenesis. Here we have placed the entire mouse locus under the control of a human PWS-IC by targeted replacement of the mouse PWS-IC with the equivalent human region. Paternal inheritance of the human PWS-IC demonstrates for the first time that a positive regulatory element in the PWS-IC has diverged. These mice show postnatal lethality and growth deficiency, phenotypes not previously attributed directly to the affected genes. Following maternal inheritance, the human PWS-IC is able to acquire a methylation imprint in mouse oocytes, suggesting that acquisition of the methylation imprint is conserved. However, the imprint is lost in somatic cells, showing that maintenance has diverged. This maternal imprinting defect results in expression of maternal Ube3a-as and repression of Ube3a in cis, providing evidence that Ube3a is regulated by its antisense and creating the first reported mouse model for AS imprinting defects. 相似文献
6.
7.
Keiko Kishimoto Jun Nomura Jacob Ellegood Keita Fukumoto Jason P. Lerch Daniel Moreno‐De‐Luca Thomas Bourgeron Kota Tamada Toru Takumi 《Genes to cells : devoted to molecular & cellular mechanisms》2017,22(5):436-451
Duplications of human chromosome 2q13 have been reported in patients with neurodevelopmental disorder including autism spectrum disorder. Nephronophthisis‐1 (NPHP1) was identified as a causative gene in the minimal deletion on chromosome 2q13 for familial juvenile type 1 nephronophthisis and Joubert syndrome, an autosomal recessive neurodevelopmental disorder characterized by a cerebellar and brain stem malformation, hypotonia, developmental delay, ataxia, and sometimes associated with cognitive impairment. NPHP1 encodes a ciliary protein, nephrocystin‐1, which is expressed in the brain, yet its function in the brain remains largely unknown. In this study, we generated bacterial artificial chromosome‐based transgenic mice, called 2q13 dup, that recapitulate human chromosome 2q13 duplication and contain one extra copy of the Nphp1 transgene. To analyze any behavioral alterations in 2q13 dup mice, we conducted a battery of behavioral tests. Although 2q13 dup mice show no significant differences in social behavior, they show deficits in spontaneous alternation behavior and fear memory. We also carried out magnetic resonance imaging to confirm whether copy number gain in this locus affects the neuroanatomy. There was a trend toward a decrease in the cerebellar paraflocculus of 2q13 dup mice. This is the first report of a genetic mouse model for human 2q13 duplication. 相似文献
8.
9.
Human PEG1/MEST, an imprinted gene on chromosome 7 总被引:10,自引:3,他引:10
Kobayashi S; Kohda T; Miyoshi N; Kuroiwa Y; Aisaka K; Tsutsumi O; Kaneko- Ishino T; Ishino F 《Human molecular genetics》1997,6(5):781-786
The mouse Peg1/Mest gene is an imprinted gene that is expressed
particularly in mesodermal tissues in early embryonic stages. It was the
most abundant imprinted gene among eight paternally expressed genes (Peg
1-8) isolated by a subtraction-hybridization method from a mouse embryonal
cDNA library. It has been mapped to proximal mouse chromosome 6, maternal
duplication of which causes early embryonic lethality. The human
chromosomal region that shares syntenic homology with this is 7q21-qter,
and human maternal uniparental disomy 7 (UPD 7) causes apparent growth
deficiency and slight morphological abnormalities. Therefore, at least one
paternally expressed imprinted gene seems to be present in this region. In
this report, we demonstrate that human PEG1/MEST is an imprinted gene
expressed from a paternal allele and located on chromosome 7q31-34, near
D7S649. It is the first imprinted gene mapped to human chromosome 7 and a
candidate for a gene responsible for primordial growth retardation
including Silver-Russell syndrome (SRS).
相似文献
10.
A member of the MAP kinase phosphatase gene family in mouse containing a complex trinucleotide repeat in the coding region 总被引:1,自引:1,他引:1
Theodosiou AM; Rodrigues NR; Nesbit MA; Ambrose HJ; Paterson H; McLellan- Arnold E; Boyd Y; Leversha MA; Owen N; Blake DJ; Ashworth A; Davies KE 《Human molecular genetics》1996,5(5):675-684
11.
The Dlx5 and Dlx6 homeobox genes are essential for craniofacial,axial, and appendicular skeletal development 总被引:7,自引:0,他引:7
Dlx homeobox genes are mammalian homologs of the Drosophila Distal-less (Dll) gene. The Dlx/Dll gene family is of ancient origin and appears to play a role in appendage development in essentially all species in which it has been identified. In Drosophila, Dll is expressed in the distal portion of the developing appendages and is critical for the development of distal structures. In addition, human Dlx5 and Dlx6 homeobox genes have been identified as possible candidate genes for the autosomal dominant form of the split-hand/split-foot malformation (SHFM), a heterogeneous limb disorder characterized by missing central digits and claw-like distal extremities. Targeted inactivation of Dlx5 and Dlx6 genes in mice results in severe craniofacial, axial, and appendicular skeletal abnormalities, leading to perinatal lethality. For the first time, Dlx/Dll gene products are shown to be critical regulators of mammalian limb development, as combined loss-of-function mutations phenocopy SHFM. Furthermore, spatiotemporal-specific transgenic overexpression of Dlx5, in the apical ectodermal ridge of Dlx5/6 null mice can fully rescue Dlx/Dll function in limb outgrowth. 相似文献
12.
Okamura K Hagiwara-Takeuchi Y Li T Vu TH Hirai M Hattori M Sakaki Y Hoffman AR Ito T 《Genome research》2000,10(12):1878-1889
Mouse Impact is a paternally expressed gene encoding an evolutionarily conserved protein of unknown function. Here we identified IMPACT, the human homolog of Impact, on chromosome 18q11. 2-12.1, a region syntenic to the mouse Impact locus. IMPACT was expressed biallelically in brain and in various tissues from two informative fetuses and in peripheral blood from an informative adult. To reveal the structural basis for the difference in allelic expression between the two species, we elucidated complete genome sequences for both mouse Impact ( approximately 38 kb) and human IMPACT ( approximately 30 kb). Sequence comparison revealed that the two genes share a well-conserved exon-intron organization but bear significantly different CpG islands. The mouse island lies in the first intron and contains characteristic tandem repeats. Furthermore, this island serves as a differentially methylated region (DMR) consisting of a hypermethylated maternal allele and an unmethylated paternal allele. Intriguingly, this intronic island is missing from the nonimprinted human IMPACT, whose sole CpG island spans the first exon, lacks any apparent repeats, and escapes methylation on both chromosomes. These results suggest that the intronic DMR plays a role in the imprinting of Impact. 相似文献
13.
Syntenic organization of the mouse distal chromosome 7 imprinting cluster and the Beckwith-Wiedemann syndrome region in chromosome 11p15.5 总被引:8,自引:2,他引:8
Paulsen M; Davies KR; Bowden LM; Villar AJ; Franck O; Fuermann M; Dean WL; Moore TF; Rodrigues N; Davies KE; Hu RJ; Feinberg AP; Maher ER; Reik W; Walter J 《Human molecular genetics》1998,7(7):1149-1159
In human and mouse, most imprinted genes are arranged in chromosomal
clusters. Their linked organization suggests co-ordinated mechanisms
controlling imprinting and gene expression. The identification of local and
regional elements responsible for the epigenetic control of imprinted gene
expression will be important in understanding the molecular basis of
diseases associated with imprinting such as Beckwith- Wiedemann syndrome.
We have established a complete contig of clones along the murine imprinting
cluster on distal chromosome 7 syntenic with the human imprinting region at
11p15.5 associated with Beckwith- Wiedemann syndrome. The cluster comprises
approximately 1 Mb of DNA, contains at least eight imprinted genes and is
demarcated by the two maternally expressed genes Tssc3 (Ipl) and H19 which
are directly flanked by the non-imprinted genes Nap1l4 (Nap2) and Rpl23l
(L23mrp), respectively. We also localized Kcnq1 (Kvlqt1) and Cd81 (Tapa-1)
between Cdkn1c (p57(Kip2)) and Mash2. The mouse Kcnq1 gene is maternally
expressed in most fetal but biallelically transcribed in most neonatal
tissues, suggesting relaxation of imprinting during development. Our
findings indicate conserved control mechanisms between mouse and human, but
also reveal some structural and functional differences. Our study opens the
way for a systematic analysis of the cluster by genetic manipulation in the
mouse which will lead to animal models of Beckwith-Wiedemann syndrome and
childhood tumours.
相似文献
14.
Discovery of a novel, paternally expressed ubiquitin-specific processing protease gene through comparative analysis of an imprinted region of mouse chromosome 7 and human chromosome 19q13.4
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Kim J Noskov VN Lu X Bergmann A Ren X Warth T Richardson P Kouprina N Stubbs L 《Genome research》2000,10(8):1138-1147
Using mouse BAC clones spanning an imprinted interval of proximal mouse chromosome 7 and the genomic sequence of the related interval of human chromosome 19q13.4, we have identified a novel mouse gene, Usp29 (ubiquitin-specific processing protease 29), near two known imprinted genes, Peg3 and Zim1. Gene Usp29 is located directly adjacent to Peg3 in a "head-to-head" orientation, and comprises exons distributed over a genomic distance of at least 400 kb. A similar human gene is also found in the homologous location in human chromosome 19q13.4. The mouse Usp29 gene is also imprinted and is transcribed mainly from the paternal allele with highest expression levels in adult brain, especially in the cerebral cortex and hippocampus, and in the forebrain, face, and limb buds of midgestation mouse embryos. Analysis of a full-length 7.6-kb cDNA clone revealed that Usp29 encodes an 869-amino-acid protein that displays significant homology with yeast and nematode ubiquitin carboxyl-terminal hydrolases. These data suggest that, like the candidate Angelman syndrome gene Ube3a (ubiquitin ligase), Usp29 may represent another imprinted gene involved in the ubiquitination pathway. This identification of a third imprinted gene, Usp29, from the Peg3/Zim1-region confirms the presence of a conserved imprinted domain spanning at least 500 kb in the proximal portion of mouse chromosome 7 (Mmu7). 相似文献
15.
Retention of imprinting of the human apoptosis-related gene TSSC3 in human brain tumors 总被引:3,自引:0,他引:3
Müller S van den Boom D Zirkel D Köster H Berthold F Schwab M Westphal M Zumkeller W 《Human molecular genetics》2000,9(5):757-763
Genomic imprinting is the result of a gamete-specific modification leading to parental origin-specific gene expression in somatic cells of the offspring. Several embryonal tumors show loss of imprinting of genes clustered in human chromosome 11p15.5, an important tumor suppressor gene region, harboring several normally imprinted genes. TSSC3, a gene homologous to mouse TDAG51, implicated in Fas-mediated apoptosis, is also located in this region between hNAP2 and p57 (KIP2). TSSC3 is the first apoptosis-related gene found to be imprinted in placenta, liver and fetal tissues where it is expressed from the maternal allele in normal human development. This study investigated the imprinting status of TSSC3 in human normal, adult brain and in human neuroblastomas, medulloblastomas and glioblastomas. A polymorphism in exon 1 at position 54 was used to analyze the allelic expression of the TSSC3 gene by a primer oligo base extension (PROBE) assay using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). We found that the TSSC3 gene is not imprinted in human normal, adult brain and blood. In contrast, strong allelic bias resembling imprinting could be detected in most examined tumor specimens. The results demonstrate for the first time that the tumors under investigation are associated with a retention of imprinting of a potential growth inhibitory gene. 相似文献
16.
Sequence conservation and variability of imprinting in the Beckwith-Wiedemann syndrome gene cluster in human and mouse 总被引:14,自引:0,他引:14
Paulsen M El-Maarri O Engemann S Strödicke M Franck O Davies K Reinhardt R Reik W Walter J 《Human molecular genetics》2000,9(12):1829-1841
In human and mouse most imprinted genes are arranged in chromosomal clusters. This linked organization suggests coordinated mechanisms controlling imprinted expression. We have sequenced 250 kb in the centre of the mouse imprinting cluster on distal chromosome 7 and compared it with the orthologous Beckwith-Wiedemann gene cluster on human chromosome 11p15.5. This first comparative imprinting cluster analysis revealed a high structural and functional conservation of the six orthologous genes identified. However, several striking differences were also discovered. First, compared with the mouse the human sequence is approximately 40% longer, mostly due to insertions of two large repetitive clusters. One of these clusters encompasses an additional gene coding for a homologue of the ribosomal protein L26. Second, pronounced blocks of unique direct repeats characteristic of imprinted genes were only found in the human sequence. Third, two of the orthologous gene pairs Tssc4/TSSC4 and Ltrpc5/LTRPC5 showed apparent differences in imprinting between human and mouse, whereas others like Tssc6/TSSC6 were not imprinted in either organism. Together these results suggest a significant functional and structural variability in the centre of the imprinting cluster. Some genes escape imprinting in both organisms whereas others exhibit tissue- and species-specific imprinting. Hence the control of imprinting in the cluster appears to be a highly dynamic process under fast evolutionary adaptation. Intriguingly, whereas imprinted genes within the cluster contain CpG islands the non-imprinted Ltrpc5 and Tssc6/TSSC6 do not. This and additional comparisons with other imprinted and non-imprinted regions suggest that CpG islands are key features of imprinted domains. 相似文献
17.
WNTs are a family of secreted-type glycoproteins implicated in embryogenesis and carcinogenesis. We have previously cloned and characterized human WNT2B/WNT13, WNT3, WNT3A, WNT5B, WNT6, WNT7B, WNT8A, WNT8B, WNT10A, WNT10B, WNT11, WNT14, and WNT14B/WNT15. WNT14B gene is clustered with WNT3 gene in human chromosome 17q21, and mRNA expression of WNT14B is significantly up-regulated by retinoic acid during the early phase of neuronal differentiation in human NT2 cells. Here, we identified mouse Wnt14b gene fragments in mouse genome draft sequence AL596108.5 by using bioinformatics, and isolated mouse Wnt14b cDNAs by using cDNA-PCR. Mouse Wnt14b was found to encode a 359-amino-acid WNT family protein with the N-terminal signal peptide, an N-linked glycosylation site, and 24 conserved cysteine residues. Mouse Wnt14b showed 92.5% total-amino-acid identity with human WNT14B, and 64.2% total-amino-acid identity with human WNT14. Mouse Wnt14b gene, consisting of 4 exons, was clustered with mouse Wnt3 gene in mouse chromosome 11. Mouse Wnt14b mRNA was relatively highly expressed in 17-day embryo, and also expressed in adult brain, kidney, liver, 7-day embryo, and 11-day embryo. This is the first report on molecular cloning and characterization of mouse Wnt14b. 相似文献
18.
19.
Connor F; Smith A; Wooster R; Stratton M; Dixon A; Campbell E; Tait TM; Freeman T; Ashworth A 《Human molecular genetics》1997,6(2):291-300
A proportion of human breast cancers result from an inherited
predisposition to the disease. Mutations in the BRCA2 gene confer a high
risk of breast cancer and are responsible for almost half of these cases.
The recent cloning of the human BRCA2 gene has revealed that it encodes a
large protein having little significant homology to known proteins. Here we
describe the mouse Brca2 gene. The gene maps to mouse chromosome 5,
consistent with its location on human chromosome 13q12. We have sequenced
cDNA for the entire 3329 amino acid Brca2 protein and this has revealed
that, like Brca1, Brca2 is relatively poorly conserved between humans and
mice. Brca2 is transcribed in a diverse range of mouse tissues, and the
pattern of expression is strikingly similar to that of Brca1. Taken
together, our data highlight some intriguing similarities between two genes
involved in inherited breast cancer susceptibility.
相似文献