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20 records found


Taxon: Human

Chromosome: 15

Location:

Gene: UPD

Description: Approximately 2-3% of Angelman syndrome (AS) cases are caused by paternal uniparental disomy of chromosome 15. Characteristic features include severe mental retardation, absence of speech, seizures and a happy disposition with unmotivated laughter. There are some reports that the UPD 15 AS phenotype is milder than that of AS caused by deletions in UBE3A, while there have also been conflicting reports that some cases may infact be more severe (Poyatos D et al. 2002). UPD and 15q11-q13 imprinting defects however produce phenotypes which are clinically indistinguishable suggesting that this region contains the only imprinted regions on chromosome 15 relevant to Angelman Syndrome (Lossie AC et al. 2001).
Twenty-five to thirty percent of Prader-Willi cases result from maternal uniparental disomy of chromosome 15 (Glenn CC et al. 1997).

Category: Disomy (UPD)

Links: Record:454 Last Modified 9/27/2007

Taxon: Human

Chromosome: 15

Location: 15q11-q13 (0)

Gene: "Prader-Willi syndrome" (PWS)

Description: Prader-Willi syndrome (PWS) is a contiguous gene syndrome involving several imprinted genes in 15q11-q13 which can occur by three different molecular mechanisms, ie, large deletions (70-75%), maternal UPD (25-30%), or imprinting mutations (2-5%) (Glenn CC et al, 1997; Nicholls RD, 1998; Nicholls RD and Knepper JL, 2001; Bittel DC, Butler MG, 2004). See individual entries for 15q.
Cases of PWS having microdeletion suggest that loss of SNORD116@ (the HBII-85 cluster) and/or SNORD19A (HBII-438A) snoRNAs cause the key characteristics of PWS (Sahoo T et al, 2008; Gallagher RC et al, 2002; de Smith et al, 2009; Duker AL et al, 2010). Studies on a family with complete deletion of the HBII-52 cluster have excluded a major role for this cluster in PW (Runte M et al, 2004).
Deletion of murine MBII-85 snoRNA (equivalent to human SNORD116@, small nucleolar RNA, C/D box 116 cluster) caused postnatal growth retardation, with about 15% postnatal lethality indicating a functional role for the MBII-85 snoRNA (Skryabin BV et al 2007).
The mouse phenotype resulting from disruption of Necdin suggests a role for human NDN in PWS (Muscatelli F et al, 2000).
Some of the phenotypic features of Magel2 knockout mice resemble Prader-Willi syndrome features (neonatal growth retardation, excessive weight gain after weaning, and increased adiposity with altered metabolism in adulthood) (Bischof JM et al, 2007).

Category: Imprinting disorder

Links: OMIM    Record:43 Last Modified 1/27/2017

Taxon: Human

Chromosome: 15

Location: 15q11-q13 (00)

Gene: "Angelman syndrome"

Description: Angelman syndrome is caused by loss of expression (in the brain) of the imprinted (maternally expressed) gene, UBE3A. UBE3A function can be disrupted by paternal UPD (1-2% of cases), maternal deletion (75%), loss of methylation at the SNURF TSS-DMR (~3%) and mutations of UBE3A itself (5-10%) (Soellner L et al 2017).
Angelman syndrome is characterised by microcephaly, seizures, ataxia, muscular hypotonia and motor delay (Buiting K et al 2016).

Category: Imprinting disorder

Links: OMIM    Record:180 Last Modified 1/30/2017

Taxon: Human

Chromosome: 15

Location: 15q11-q13 (01)

Gene: MKRN3 (ZNF127)

Description: MKRN3 (Makorin3, ZNF127) is paternally expressed and putatively encodes a 505 amino acid polypeptide-containing zinc-finger motif (Jong MTC et al 1999; Glenn CC et al, 1997; Glenn CC et al, 1993; Driscoll DJ et al, 1992).
Mutations of MKRN3 are associated with precocious puberty when paternally inherited (Abreu AP et al, 2013; Simon D et al, 2016).
An antisense transcript MKRN3-AS1 (ZNF127AS, FNZ127, DN34) has been reported but its imprinting status is not yet known (Jong MTC et al, 1999): the mouse homologue Mkrn3os (Zfp127as) is reported to be paternally expressed.

Category: Imprinted genes

Links: GENE   Record:44 Last Modified 3/7/2016

Taxon: Human

Chromosome: 15

Location: 15q11-q13 (02)

Gene: MAGEL2 (NDNL1)

Description: MAGEL2 (a member of the MAGE gene superfamily) is expressed exclusively from the paternal allele in adult brain and fibroblasts (Boccaccio I et al, 1999; Lee S et al, 2000).
Some of the phenotypic features of Magel2 knockout mice resemble Prader-Willi syndrome features (neonatal growth retardation, excessive weight gain after weaning, and increased adiposity with altered metabolism in adulthood) (Bischof JM et al, 2007).
Baran Y et al (2015) found evidence of imprinting of MAGEL2 (using RNA-seq) in adult brain and pituitary tissues.

Category: Imprinted genes

Links: Gene   Record:189 Last Modified 8/3/2017

Taxon: Human

Chromosome: 15

Location: 15q11-q13 (03)

Gene: NDN

Description: NDN (Necdin (mouse) homologue) is paternally expressed in brain (human and mouse) and fibroblasts. It is expressed in differentiated neurones (MacDonald HR et al, 1997; Jay P et al, 1997; Watrin F et al, 1997).
Bisulfite sequencing revealed a bias towards maternal allele-specific DNA hypermethylation of the promoter CpG island of NDN, independent of tissue-specific transcriptional activity (Lau C.Y.J et al, 2004).

Category: Imprinted genes

Links: Gene   Record:45 Last Modified 4/14/2014

Taxon: Human

Chromosome: 15

Location: 15q11-q13 (04)

Gene: PWRN2

Description: PWRN2 (Prader-Willi region non-protein coding RNA 2) was reported to be expressed only in testis and biallelic (Buiting K et al, 2007).
A difference of 23% in DNA methylation values between normal human ESCs and parthenogenic human induced pluripotent stem cells was consistent with the presence of an associated DMR (Stelzer Y et al, 2013).

Category: Other

Links: Gene   Record:1371 Last Modified 4/14/2014

Taxon: Human

Chromosome: 15

Location: 15q11-q13 (05)

Gene: W89101 (provisional)

Description: W89101, a singleton EST 595 kb upstream of SNRPN showed consistent preferential paternal expression from mouse A9 hybrid cells that contained either a single paternal or single maternal chromosome 15 (Meguro M et al, 2001).
In GRCh38/hg38, W89101 remains a singleton EST.

Category: Other

Links: Nucleotide   Record:1064 Last Modified 10/26/2015

Taxon: Human

Chromosome: 15

Location: 15q11-q13 (06)

Gene: PWRN1

Description: PWRN1 (prader-willi region non-protein-coding RNA 1), which is located 265 kb upstream of SNRPN, was biallelically expressed in testis and kidney, but monoallelically in 2 fetal brains. Parent-of-origin could not be determined (Buiting K et al, 2007).
Baran Y et al (2015) found evidence of imprinting of PWRN1 (using RNA-seq) in adult brain, pituitary and thyroid tissues. Allelic expression of PWRN1 in other tissues was also consistent with imprinting (adrenal gland, transverse colon, ovary, pancreas, prostate and stomach). Biallelic expression of PWRN1 was observed in testis tissue.

Category: Imprinted genes

Links: Gene   Record:1261 Last Modified 8/3/2017

Taxon: Human

Chromosome: 15

Location: 15q11-q13 (07)

Gene: NPAP1 (C15orf2)

Description: NPAP1 (nuclear pore associated protein 1; C15orf2) is located 149 kb upstream of SNRPN. In one sample NPAP1 was monoallelically expressed in fetal brain and expressed from the paternal allele (Wawrzik M et al, 2010). NPAP1 protein was present in several regions of the adult brain including the hypothalamus. An orthologous gene is not present in mice.

Several piRNAs overlap NPAP1 in the sense orientation (Buiting K et al, 2007). These include piR-38677, piR-35312 and piR-30791.
Note: in view of its location it is likely that NPAP1 is imprinted.

Category: Imprinted genes

Links: Gene   Record:1253 Last Modified 4/14/2014

Taxon: Human

Chromosome: 15

Location: 15q11-q13 (08)

Gene: SNHG14 (SNURF, SNRPN, SNORD107 (HBII-436), SNORD64 (HBII-13), SNORD108(HBII-437), SNORD109A (HBII438A), SNORD116@ (PWCR1; HBII-85), SNORD115@ (HBII-52), SNORD109B (HBII438B), UBE3A-AS (incl. IPW,PAR-SN,PAR1,PAR5))

Description: The SNHG14 small nucleolar RNA host gene 14 transcript extends from SNURF to UBE3A (antisense) and spans 460 kb and 148 exons (Nicholls RD et al, 2001; Runte M et al, 2001). It is exclusively paternally expressed and contains:
An imprinting centre (IC) at its 5' end;
SNURF (SNRPN Upstream Reading Frame) that is encoded by exons 1-3 (Gray TA et al, 1999);
SNRPN (small nuclear ribonucleoprotein polypeptide N) that is encoded by exons 4-10 (Glenn CC et al, 1993; Sutcliffe JS et al, 1994);
Small nucleolar RNAs (snoRNAs) SNORD107 (HBII-436), SNORD64 (HBII-13), SNORD108(HBII-437), SNORD109A (HBII438A), SNORD116@ (PWCR1; 24 copies of HBII-85), SNORD115@ (47 copies of HBII-52), and SNORD109B (HBII438B) which are encoded within the introns (Cavaille J et al, 2000; Runte M et al, 2001; de los Santos T et al, 2000);
IPW, a long noncoding RNA in the critical region of the PWS locus (it is also a regulator of the DLK1-DIO3 imprinted region) (Wevrick R et al, 1994; Stelzer Y et al, 2014);
And finally UBE3A-AS, the paternally expressed UBE3A antisense transcript (Rougeulle C et al, 1998) that is thought to control the imprinting of UBE3A (Martins-Taylor K et al, 2014).
The extended transcript includes PAR-SN (Ning Y et al, 1996), PAR1 and PAR5 (Sutcliffe JS et al, 1994).

The transcript extends beyond SNORD116 in neurons but not in non-neuronal cells (Lee S et al, 2003; Runte M et al, 2004 ).
The germline imprint control region (DMR) overlaps exon 1 of SNRPN (Zeschnigk M et al, 1997).

Using mouse A9 hybrids containing a single paternal or maternal chromosome, biased paternal expression was found for the following ESTs within this extended transcript: H20970, R37082, R42946, H59928, N21972, H17549, H75355 (Meguro M et al, 2001).

Baran Y et al (2015) found evidence of imprinting of SNURF (using RNA-seq) in multiple adult tissues (subcutaneous adipose, adrenal gland, aorta, coronary artery, tibial artery, brain, mammary tissue, transverse colon, oesophagus muscularis, transformed fibroblasts, atrial appendage, left ventricle, EBV-transformed lymphocytes, lung, skeletal muscle, tibial nerve, ovary, pituitary, not sun exposed skin, sun exposed skin, stomach, thyroid, uterus and T cells). Allelic expression of SNURF in multiple other tissues was also consistent with imprinting (pancreas, prostate, visceral adipose, vagina, fallopian tube, whole blood, liver and oesophagus mucosa). Biallelic expression of SNURF was observed in testis tissue.

Category: Imprinted genes

Links: Gene   Record:47 Last Modified 9/18/2018

Taxon: Human

Chromosome: 15

Location: 15q11-q13 (10)

Gene: UBE3A

Description: UBE3A (ubiquitin protein ligase E3A) is maternally expressed in human and mouse brain, but is biallelically expressed in other tissues. This gene is mutated in some cases of Angelman syndrome, deleted in others (60-70%), and affected by paternal UPD in others (Rougeulle C et al, 1997; Vu TH et al, 1997). UBE3A has a downstream transcript which shows predominant maternal expression (Rougeulle C et al, 1998).
Morcos L et al (2011) found no evidence of allelic expression bias in lymphoblast and fibroblast cell lines.
UBE3A antisense transcript (UBE3A-ATS) is thought to control the imprinting of UBE3A (Martins-Taylor K et al, 2014).

Category: Imprinted genes

Links: Gene   Record:52 Last Modified 2/10/2017

Taxon: Human

Chromosome: 15

Location: 15q11-q13 (20)

Gene: "Autism"

Description: Abnormalities (duplications and deletions) of chromosome 15q have been implicated in autism. In nearly all cases, the deletions or duplications have occurred on the chromosome inherited from the mother (Boyar FZ et al, 2001; Bolton PF et al, 2001; Cook EH et al. 1997; Schroer RJ et al. 1998; Repetto GM et al. 1998; Woods CG et al Am J Hum Genet 1997;61:A117; Autism Genome Project Consortium, 2007).
Transmission disequilibrium tests between autism and SNPs within ATP10A showed evidence of parent-specific transmission. Three SNPs showed maternal-specific transmission whereas one showed paternal specific transmission (Nurmi EL et al. 2003).

Category: Parental effect

Links: OMIM    Record:54 Last Modified 4/30/2010

Taxon: Human

Chromosome: 15

Location: 15q11.2

Gene: ATP10A (ATP10C)

Description: ATP10A (ATPase, Class V, type 10A; aminophospholipid-transporting ATPase, ATP10C) shows preferential maternal expression in human brain and lymphoblasts. It is 400 kb distal to UBE3A (Meguro M et al, 2001, Herzing LBK et al, 2001).
Hogart A et al (2008) found monoallelic expression of ATP10A in brain, but their findings implicated factors other than imprinting.
Morcos L et al (2011) found no evidence of allelic expression bias in lymphoblast and fibroblast cell lines.
Baran Y et al (2015) found no evidence of imprinting of ATP10A in multiple adult tissues (using RNA-seq).

Category: Other

Links: Gene   Record:260 Last Modified 8/3/2017

Taxon: Human

Chromosome: 15

Location: 15q11.2

Gene: "BP1-BP2 microdeletion (Burnside-Butler) syndrome (chromosome 15q11.2 deletion syndrome)"

Description: BP1-BP2 microdeletion (Burnside-Butler) syndrome (chromosome 15q11.2 deletion syndrome) presents with a wide range of findings including cognitive deficits, language and/or motor delays, autism spectrum disorder, behavioural disturbances, poor coordination, ataxia, attention disorders, seizures, and dysmorphic or congenital anomalies. In an analysis of 15 clinical features, the parent-of-origin of the deletion was different in three: paternally inherited deletions were associated with congenital heart disease (22% vs. 0%, p = 0.004); maternally inherited deletions were associated with macrocephaly (15% vs. 0%, p = 0.016) and autism spetrum disorder (29% vs. 8%, p = 0.02) (Davis KW et al, 2019).

Category: Parental effect

Links: OMIM   Record:1504 Last Modified 7/22/2019

Taxon: Human

Chromosome: 15

Location: 15q11.2-q13

Gene: GABRB3, GABRA5, GABRG3 (conflicting data)

Description: The GABAA receptor subunit gene expression was detected from mouse A9 hybrids containing a single human paternal chromosome 15, but not from cells containing a maternal chromosome 15, leading to the conclusion that human GABRB3, GABRA5, GABRG3 are imprinted (paternally expressed). Unexpectedly there was evidence of paternal methylation at the 5 end of GABRB3 (Meguro M et al, 1997). Previously Kubota T et al (1994) reported possible paternal silencing of GABRB3 on the basis of undetectable expression in a single hydatidiform mole.
Presence of a 50-60 kb domain of allele-specific replication between the γ-aminobutyric acid receptor subunit β3 (GABRB3) and α5 (GABRA5) genes were reported (LaSalle M J and Lalande M, 1994)
All three genes were biallelically expressed in 21 brain samples (Hogart A et al, 2007).
Reduced expression levels of GABRA5 and GABRB3, measured by microarray and quantitative RT-PCR, were noted in cells from PWS with maternal UPD suggesting higher expression levels from the paternal allele (Bittel DC et al, 2003).
GABRB3 showed significantly reduced expression in multiple Rett, Angelman and autism human brain samples and in Mecp2 deficient mice, by quantitative immunoblot suggesting that the reduced levels of GABRB3 were attributable to altered neuronal function rather than imprinting (Samaco RC et al, 2005).
Transmission disequilibrium test analysis has provided evidence for paternal (but not maternal) transmission of GABRA5 and GABRB3 in association with alcoholism (P < 0.004 and P < 0.007 respectively) (Jiuzhou S et al, 2003). In contrast others have failed to confirm any parent-or-origin effects for alcoholism at this locus (Dick DM et al, 2004).
Morcos L et al (2011) found no evidence of allelic expression bias in fibroblast cell lines for GABRB3 and GABRA5 and for GABRG3 no evidence of imprinting was found in the lymphoblast cell lines investigated.

Category: Other

Links: OMIM (GABRB3)   OMIM (GABRA5)   OMIM (GABRG3)   Gene (GABRB3)   Gene (GABRA5)   Gene (GABRG3)   Record:420 Last Modified 5/26/2013

Taxon: Human

Chromosome: 15

Location: 15q13

Gene: H73492 (Hs.268983) (provisional)

Description: A transcript, H73492, that had been assigned, in error, to the PWS/AS critical region (D15S1035-D15S165), showed preferential paternal expression in monochromosomal mouse A9 hybrids retaining either a paternal or maternal copy of human chromosome 15 (Meguro M et al, 2001). H73492 exists in two copies within a large recent segmental duplication (Riley B et al, 2002).

Category: Imprinted genes

Links: Nucleotide   Record:439 Last Modified 8/10/2006

Taxon: Human

Chromosome: 15

Location: 15q24

Gene: RASGRF1 (GRF1)

Description: Rasgrf1 is paternally expressed and paternally methylated in mouse. Yuen RK et al (2011) reported maternal-specific methylation in the placental mesenchyme. Expression studies were not informative.

Category: Other

Links: Gene   Record:192 Last Modified 8/1/2016

Taxon: Human

Chromosome: 15

Location: 15q26.3

Gene: Alcoholism

Description: Using the COGA dataset released for the Genetic Analysis Workshop 14, evidence for a possible maternal linkage effect for alcoholism was detected at 127 cM on chromosome 15 (Strauch K et al, 2005).

Category: Parental effect

Links: Record:1029 Last Modified 7/2/2006

Taxon: Human

Chromosome: 15

Location: 15q26.3

Gene: IRAIN (IGF1R-AS) (provisional data)

Description: IRAIN (IGF1R antisense imprinted non-protein coding RNA, IGF1R-AS), a 5.3 kb antisense transcript originating in intron 1 of IGF1R, showed monoallelic paternal expression in five informative peripheral blood samples (Sun J et al, 2014; Kang L et al, 2015).
Monoallelic expression was detected in 18 breast cancers, in three additional blood samples, in KG-1 and KG-1a haematopoietic cell lines, and in MCF-7 breast cancer cells (Kang L et al, 2015).
At its promoter region, the CpG island showed methylated and unmethylated alleles in one normal haematopoietic stems cell sample, in KG-1 cells, in three acute myeloid leukaemia samples, and in two breast cancer samples, but dense methylation of all alleles for K562 cells and total unmethylation in MCF-7 and MDA-MB-231 breast cancer cell lines, in four breast cancer samples and in three blood samples (Sun J et al, 2014; Kang L et al, 2015).
The allele usage is interesting in that in 23 of 26 samples the expressed allele was the "A" allele (Sun J et al, 2014; Kang L et al, 2015).
Another unusual feature is that in two breast cancers the expressed allele was the "G" allele while in the blood from the same patients that "A" allele was expressed (Kang L et al, 2015). This allele switching together with the non-statistically significant number of cases (5) in which paternal expression was documented, suggest that the imprinting status of IRAIN should be regarded as provisional.

Category: Imprinted genes

Links: Gene   Record:1399 Last Modified 1/8/2016

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