Two Novel Genes in the Center of the 11p15 Imprinted Domain Escape Genomic Imprinting

Lee, Maxwell P.; Brandenburg, Sheri A.; Landes, Gregory M.; Adams, Mark D.; Miller, Glenn A.; Feinberg, Andrew P.

doi:10.1093/hmg/8.4.683

Cited by 67 publications

(52 citation statements)

References 24 publications

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“…The TH gene has been isolated and mapped to chromosome 11p15.5 (Craig et al 1986;Moss et al 1986). This region contains at least seven imprinted genes (Lee et al 1999) which is intriguing, as imprinted genes tend to cluster. Also, the 5Ј flanking region of the TH gene is known to be methylated (Okuse et al 1997), methylation being a putative process involved in imprinting.…”

Section: Integrating Our Results With Existing Workmentioning

confidence: 99%

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Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

Kirley

Hawi

Daly

et al. 2002

Neuropsychopharmacology

106

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Converging evidence has implicated abnormalities of dopamine neurotransmission to the pathology of attention deficit hyperactivity disorder (ADHD).Attention Deficit Hyperactivity Disorder (ADHD) is a common condition of childhood affecting 3-6% of school age children worldwide (Barkley 1990), with males being affected three times more than females (Anderson et al. 1987; Baumgartel et al. 1995). Its core clinical features include excessive motor activity, impaired attention, and impulsivity. ADHD causes marked educational, social, and family difficulties for sufferers and their relatives. The condition is of early onset (usually before age 7) and tends to persist throughout childhood. Moreover, approximately 30-60% of children with ADHD have persisting psychopathology in adulthood (Gittelman et al. 1985;Weiss and Hechtman 1986; Barkley 1990;Swanson et al. 1998a). The exact etiology of ADHD is Received March 8, 2001; revised February 12, 2002; accepted February 20, 2002. Online publication: 2/28/02 at www.acnp.org/citations/ Npp022802254. 608 A. Kirley et al. N EUROPSYCHOPHARMACOLOGY 2002 -VOL . 27 , NO . 4 unknown, but a substantial genetic element exists. This has been demonstrated by family (Biederman et al. 1990(Biederman et al. , 1992Faraone et al., 1992Faraone et al., , 1994, twin (Thapar et al. 1995;Silberg et al. 1996;Levy et al. 1997), and adoption studies (Alberts-Corush et al. 1986; Cadoret and Stewart 1991). The heritability (h 2 ) of ADHD has been estimated to be .50-.98 (Gjone et al. 1996;Levy et al. 1997). The exact mode of transmission remains unknown. Segregation analyses (Morrison and Steward 1974;Deutsch et al. 1990, Faraone et al. 1992, Hess et al. 1995 have proposed models of inheritance from major gene effects through oligogenic to polygenic and multifactorial models, but the differences in statistical "fit" between multifactorial genetic models and single gene inheritance is modest. The multifactorial concept is consistent with ADHD's high population prevalence (2-7%), high concordance in monozygotic twins (68-81%), but modest recurrence risks to first-degree relatives.Dysregulation in catecholamine neurotransmission is implicated in the pathophysiology of ADHD (Faraone and Biederman 2002). The dopaminergic neurotransmitter system has been most extensively studied. This article will focus mainly on its role in the etiology of ADHD. Evidence to support dopaminergic dysfunction in ADHD derives from three research areas: the neuropharmacology of stimulant medication (Zametkin and Rapoport 1987; Amara and Kuhar 1993), the behavior and biochemistry of animal models (Giros et al. 1996;Gainetdinov et al. 1999, Russell 2000, and neuroimaging studies in ADHD adults (Dougherty et al. 1999, Krause et al. 2000, and Faraone and Biederman 2002. For this reason, many molecular genetic studies have focused on dopamine system genes.The gene encoding the dopamine transporter, DAT1, was the initial candidate gene studied. This gene is of particular interest, as the transporter is the principal target...

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Section: Integrating Our Results With Existing Workmentioning

confidence: 99%

mentioning

confidence: 99%

Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

Kirley

Hawi

Daly

et al. 2002

Neuropsychopharmacology

106

View full text Add to dashboard Cite

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“…Genes subject to genomic imprinting are typically clustered in a region of hundreds of kilobases (Greally et al, 1998;Lee et al, 1999;Rainier et al, 1993). One of these regions is located on chromosome 11p15 and contains a large domain of imprinted genes with growth-promoting (IGF2) and control (p57 kip2 and H19) functions (Chung et al, 1996;Dao et al, 1999;Lee et al, 1999;Sabbioni et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…One of these regions is located on chromosome 11p15 and contains a large domain of imprinted genes with growth-promoting (IGF2) and control (p57 kip2 and H19) functions (Chung et al, 1996;Dao et al, 1999;Lee et al, 1999;Sabbioni et al, 1997). IGF2, a 67-amino acid peptide, is a paternally expressed insulinlike growth factor with autocrine growth function.…”

Section: Introductionmentioning

confidence: 99%

Frequent loss of imprinting at the IGF2 and H19 genes in head and neck squamous carcinoma

et al. 1999

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Genomic imprinting is an inherited epigenetic phenomenon that results in parental ± origin ± speci®c gene expression in somatic cells. Relaxation or loss of this feature in certain genes has been demonstrated in several pediatric and adult neoplasms, suggesting an association with tumorigenesis. We analysed 64 primary untreated head and neck squamous carcinoma for the loss of imprinting in the IGF2 and H19 genes to determine the implications of this alteration in the development and progression of these tumors. Forty-nine (77%) of the 64 tumors were informative for imprinting analyses of these genes. IGF2 and H19 were imprinted in all normal squamous epithelium examined. Twelve (37.5%) of 32 tumors informative for H19 and 11 (40.7%) of 27 tumors informative for IGF2 manifested loss of imprinting. Ten tumors were informative for both genes, of which four maintained the constitutional imprinting and six showed loss of imprinting at either H19 or IGF2. These data suggest that loss of imprinting at the IGF2 and H19 loci play a role in the oncogenesis of head and neck carcinoma.

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“…In particular, we and others have found that human chromosomal band 11p15 contains at least eight imprinted genes concentrated in an ∼1-Mb domain, of which six are expressed from the maternal allele and two are expressed from the paternal allele (Feinberg 1999). The organization of this domain is somewhat complicated in that we have identified two separate subdomains that are imprinted, separated by a region of three genes that appear to escape imprinting (Lee et al 1998(Lee et al , 1999. The boundaries of the overall 11p15 imprinted domain are known at both centromeric and telomeric ends because of the presence of at least eight nonimprinted genes that extend beyond the imprinted domain, including NAP2 and NUP98 on the centromeric side, and L23MRP and CTDS on the telomeric side (Rachmilewitz et al 1993;Tsang et al 1995;Hu et al 1996Hu et al , 1997Zubair et al 1997).…”

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confidence: 99%

Sequence and Comparative Analysis of the Mouse 1-Megabase Region Orthologous to the Human 11p15 Imprinted Domain

et al. 2000

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A major barrier to conceptual advances in understanding the mechanisms and regulation of imprinting of a genomic region is our relatively poor understanding of the overall organization of genes and of the potentially important cis-acting regulatory sequences that lie in the nonexonic segments that make up 97% of the genome. Interspecies sequence comparison offers an effective approach to identify sequence from conserved functional elements. In this article we describe the successful use of this approach in comparing a ∼1-Mb imprinted genomic domain on mouse chromosome 7 to its orthologous region on human 11p15.5. Within the region, we identified 112 exons of known genes as well as a novel gene identified uniquely in the mouse region, termed Msuit, that was found to be imprinted. In addition to these coding elements, we identified 33 CpG islands and 49 orthologous nonexonic, nonisland sequences that met our criteria as being conserved, and making up 4.1% of the total sequence. These conserved noncoding sequence elements were generally clustered near imprinted genes and the majority were between Igf2 and H19 or within Kvlqt1.

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Two Novel Genes in the Center of the 11p15 Imprinted Domain Escape Genomic Imprinting

Cited by 67 publications

References 24 publications

Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

Frequent loss of imprinting at the IGF2 and H19 genes in head and neck squamous carcinoma

Sequence and Comparative Analysis of the Mouse 1-Megabase Region Orthologous to the Human 11p15 Imprinted Domain

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