Imprinted Gene Catalogue Banner

21 records found


Taxon: Human

Chromosome: 14

Location:

Gene: "UPD"

Description: Maternal heterodisomy and isodisomy (>28 cases in literature) is associated with a characteristic phenotype similar to that of Prader-Willi syndrome (hypotonia, motor developmental delay, mild dysmorphic facial features, low birth weight, growth abnormalities (precocious puberty) (Kamnasaran D et al. 2001; Ledbetter DH et al. 1995; Hurst LD et al. 1997; Tomkins DJ et al. 1996; Kotzot D, 2007; Kagami M et al, 2008; Ogata T et al, 2008; Aretz S et al, 2005; Hosoki K et al, 2009).

Paternal isodisomy or heterodisomy of chromosome 14 (at least 17 cases) is associated with severe mental and musculoskeletal phenotype (Stevenson DA et al, 2004; Kurosawa K et al. 2002; Kamnasaran D et al. 2001; Walter CA et al. 1996; Cotter PD et al. 1997; Ogata T et al, 2008) which is recapitulated in paternal UPD of mouse chromosome 12.
Analysis of UPD14 cases suggests that imprinted genes on 14q32 are responsible for the phenotypes, but also that other imprinted regions on chr14 may exist (Kotzot D et al. 2001 for a review see Kotzot et al 2004; Sutton VR et al. 2000).

A patient with clinical features of maternal UPD14, including growth retardation, hypotonia, scoliosis, small hands and feet, and advanced puberty, had loss of methylation of the IG-DMR but no evidence of maternal UPD14 (Temple IK et al, 2007). This case suggests that the maternal UPD14 phenotype is due to aberrant gene expression within the imprinted domain at 14q32.
Quantitative real-time PCR showed that RTL1 expression level was about five times higher in the placental samples of two patients with paternal uniparental disomy 14 compared to controls, consistent with paternal expression (Kagami M et al, 2012).

Category: Disomy (UPD)

Record:42 Last Modified 10/27/2012

Taxon: Human

Chromosome: 14

Location: 14q24

Gene: TGFB3

Description: TGFB3 (transforming growth factor, beta 3) is implicated in aetiology of nonsyndromic cleft lip and palate. Reutter H et al, (2008) found strong evidence for parent-of-origin effects, with lower risk of maternal transmission compared with paternal transmission [I (M) = 0.38; confidence interval (CI): 0.17-0.86] of the risk allele T to an affected offspring at marker rs2300607.

Category: Parental effect

Links: Gene   OMIM    Record:1194 Last Modified 4/30/2010

Taxon: Human

Chromosome: 14

Location: 14q24.3-q31

Gene: Duplication phenotype

Description: A case report of dup(14q24.3-31), inherited from a phenotypically normal father, suggests that this region may be imprinted (Robin NH et al, 1997).

Category: Other

Record:41 Last Modified 4/27/2010

Taxon: Human

Chromosome: 14

Location: 14q32

Gene: Differentially methylated region

Description: This region contains a CpG island that is differentially methylated in hydatidiform moles (paternal origin) and complete ovarian teratomas (maternal origin) (Strichman-Almashanu LZ et al, 2002).

Category: DMR or ICR

Record:310 Last Modified 3/12/2015

Taxon: Human

Chromosome: 14

Location: 14q32

Gene: "Bipolar affective disorder"

Description: A putative maternally imprinted susceptibility locus for bipolar affective disorder was identified on 14q32 (Cichon S et al, 2001).

Category: Parental effect

Links: Record:386 Last Modified 4/27/2010

Taxon: Human

Chromosome: 14

Location: 14q32

Gene: miR-134, DLK1-GTL2

Description: The brain-specific microRNA miR-134 lies within the DLK1-GTL2 imprinted domain and is thought to regulate localised translation of Limk1 mRNA, which encodes a regulator for the size of dendritic spines in neurons, based on observations in the rat (Schratt GM et al, 2006). Limk1 translation is reversible by BDNF. See Royo H et al, 2008 for a review.

Category: Imprinted genes

Links: Gene   Record:1251 Last Modified 5/19/2010

Taxon: Human

Chromosome: 14

Location: 14q32

Gene: PiRNAs

Description: PiRNAs (Piwi-interacting RNAs) at 14q32 (DLK1-GTL2) are homologous with several human 14q(I) and 14(II) C/D RNA sequences (Royo H et al, 2008). No similar piRNAs have been identified at the syntenic region in rodent.

Category: Imprinted genes

Record:1254 Last Modified 6/29/2010

Taxon: Human

Chromosome: 14

Location: 14q32

Gene: MIR337

Description: MIR337 (microRNA 337, MIRN-337) was within 5 kb of an allele-specific RNA polymerase II-enriched SNP, providing evidence that this microRNA cluster is monoallelically expressed (Maynard ND et al, 2008).
Given its location and the imprinting of Mir337 in mice, it is reasonable to assume imprinting in humans.

Category: Imprinted genes

Links: Gene   Record:1404 Last Modified 1/26/2016

Taxon: Human

Chromosome: 14

Location: 14q32

Gene: Temple syndrome (TS)

Description: Temple syndrome (TS) is an imprinting disorder of chromosome 14 that has a clinical phenotype similar to that of Prader-Willi Syndrome (PWS). Individuals with TS can have short stature, intrauterine growth restriction (IUGR), precocious puberty, truncal hypotonia, motor delay, scoliosis and feeding problems in infancy (Ioannides Y et al 2014).
Imprinting at chromosome 14 occurs at 14q32. Methylation of the intergenic differentially methylated control region (IG-DMR) between DLK1 and GTL2/MEG3 on the paternal chromosome results in the expression of protein coding DLK1, RTL1 and DIO3 genes and suppression of the maternal non-coding RNA genes of GTL2/MEG3, MEG8 and RTL1as (Ioannides Y et al 2014).
In TS there is dysregulation of expression of genes at this locus. In the majority of cases (78.4%) this is due to maternal UPD of chromosome 14, resulting in overexpression of the maternally expressed genes and loss of expression of paternally expressed genes. Around 10% of cases of TS are due to a deletion of the paternal 14q32 locus and around 12% of cases are due to loss of methylation (LOM) at the MEG3/DLK1 IG-DMR and MEG3 TSS-DMR (Soellner L et al 2017).

Category: Imprinting disorder

Links: OMIM Record:1430 Last Modified 1/30/2017

Taxon: Human

Chromosome: 14

Location: 14q32

Gene: Kagami-Ogata syndrome (KOS)

Description: Kagami-Ogata Syndrome (KOS) is an imprinting disorder of chromosome 14. It is characterised by a distinctive face, a small bell-shaped thorax with a coat hanger appearance of the ribs, abdominal wall defects, placentomegally and polyhydramnios (Ogata T & Kagami M 2016).
Like Temple syndrome (TS) this disorder involves imprinted genes at 14q32. Around 65% of cases of KOS result from paternal UPD of chromosome 14, resulting in increased expression of paternally expressed genes (such as RTL1). Approximately 20% of cases are due to deletion of the maternal 14q32 locus and around 15% of cases are due to gain of methylation of the MEG3/DLK1 IG-DMR and MEG3 TSS-DMR (Soellner L et al 2017).

Category: Imprinting disorder

Links: OMIM Record:1431 Last Modified 1/30/2017

Taxon: Human

Chromosome: 14

Location: 14q32.12, 89.9 cM - 94.4 cM

Gene: Type II diabetes susceptibility locus

Description: In a genome-wide linkage analysis assessing parent-of-origin effects in the inheritance of type II diabetes in Pima Indians, a region on chromosome 14 showed evidence of linkage to maternal alleles (LOD = 1.6) but not paternal (LOD = 0) (Lindsay RS et al. 2001).

Category: Parental effect

Links: Record:445 Last Modified 9/19/2007

Taxon: Human

Chromosome: 14

Location: 14q32.2

Gene: "IG-DMR epimutation syndromes"

Description: Loss of methylation: A patient with clinical features of maternal UPD14, including growth retardation, hypotonia, scoliosis, small hands and feet, and advanced puberty, had loss of methylation of the the MEG3 promoter CpG island (which they refer to as the IG-DMR) but no evidence of maternal UPD14 (Temple IK et al, 2007). This case provided support for the hypothesis that the maternal UPD14 phenotype is due to aberrant gene expression within the imprinted domain at 14q32.
Gain of methylation: Three cases with methylation of the normally unmethylated maternal allele of IG-DMR showed a paternal-UPD(14)-like phenotype (Kagami M et al, 2008).

Category: Other

Record:1135 Last Modified 7/13/2011

Taxon: Human

Chromosome: 14

Location: 14q32.2

Gene: Type 1 Diabetes Susceptibility Locus

Description: A genome-wide association study indicated paternally inherited risk of Type 1 Diabetes (ratio of allelic effects for paternal vs. maternal transmission = 0.75) for the rs941576 SNP (Wallace C et al, 2010). This SNP is within an MEG3 gene intron in the imprinted region of chromosome 14q32.2.

Category: Parental effect

Record:1233 Last Modified 6/27/2010

Taxon: Human

Chromosome: 14

Location: 14q32.2

Gene: "early-onset obesity", DLK1

Description: Polymorphisms within DLK1 were examined for association with early-onset obesity in 359 children (Wermter AK et al, 2008). One SNP (rs1802710 T/C) within exon 5 showed increased paternal transmission of the C allele. However, relative risk for C homozygotes was not increased and leading to a hypothesis of “polar overdominance” (see callipyge sheep entry). Similar results were shown from repetition with a second cohort of 666 affected families (Wermter AK et al, 2008). No causal mutation could be identified. The rs1802710 SNP was located close to a pig polymorphism that is assoicated with decreased fat deposition (Kim K et al, 2004). For both pig and human the SNP creates a new CpG site.

Category: Parental effect

Record:1245 Last Modified 6/27/2010

Taxon: Human

Chromosome: 14

Location: 14q32.2

Gene: RTL1

Description: RTL1 (retrotransposon-like 1, Mar1, MART1, PEG11) showed allelic expression bias in fibroblast cell lines. Exclusive paternal expression was then shown in four informative parent-offspring trios (Morcos L et al (2011).
Quantitative real-time PCR showed that RTL1 expression level was about five times higher in the placental samples of two patients with paternal uniparental disomy 14 compared to controls, consistent with paternal expression (Kagami M et al, 2012).
Baran Y et al (2015) reported that allelic expression of RTL in adrenal gland, brain and pituitary tissue was consistent with imprinting (using RNA-seq).

Category: Imprinted genes

Links: Gene   Record:1315 Last Modified 8/3/2017

Taxon: Human

Chromosome: 14

Location: 14q32.2, 100.1 Mb (Mar 06)

Gene: BEGAIN (KIAA1446)

Description: Location of KIAA1446 (BEGAIN) likely ortholog of rat brain-enriched guanylate kinase-associated protein, which is imprinted (paternally expressed) in sheep (Smit MA et al, 2005).
Kagami M et al (2008) provide an incomplete comment that BEGAIN seems to be biparentally expressed.

Category: Other

Links: Gene   Record:1104 Last Modified 2/20/2008

Taxon: Human

Chromosome: 14

Location: 14q32.2, 100.26 Mb (Mar 06)

Gene: DLK1 (PEG9)

Description: DLK1 (delta, Drosophila, homolog-like 1; PEG9) encodes a transmembrane protein, and is paternally expressed. It is adjacent to the reciprocally imprinted, maternally expressed gene MEG3 (GTL2) (Wylie AA et al, 2000, Kobayashi S et al, 2000).

Category: Imprinted genes

Links: Gene   Record:226 Last Modified 10/11/2007

Taxon: Human

Chromosome: 14

Location: 14q32.2, 100.27 Mb (Mar 06)

Gene: DLK1 downstream transcripts

Description: DLK1 downstream transcripts are comparable in location to similar paternally expressed transcripts found in mouse and sheep (DAT). The imprinting status of the human transcripts has not been reported.

Category: Other

Links: UniGene   Record:499 Last Modified 9/19/2007

Taxon: Human

Chromosome: 14

Location: 14q32.2, 100.4 Mb (Mar 06)

Gene: MEG3 (GTL2)

Description: MEG3 (GTL2, maternally expressed gene 3) is maternally expressed (Miyoshi N et al, 2000). It encodes a nontranslated RNA. MEG3 and the adjacent gene DLK1 are reciprocally imprinted and the regions shows structural similarities to IGF2/H19 (Wylie AA et al, 2000).
There is paternal specific methylation upstream of MEG3 in a region that contains multiple CTCF binding sites (Rosa AL et al, 2005).
The location of the human equivalent of the mouse IG-DMR is not clear. Two DMRs have been located upstream of MEG3, referred to as CpG1 and CpG2, 15 kb and 1.7 kb upstream of MEG3 respectively (Kawakami T et al, 2006). Temple IK et al (2007) refer to methylation studies in the IG-DMR but their reported sequence is from the MEG3 promoter DMR.
Baran Y et al (2015) found evidence of imprinting of MEG3 (using RNA-seq) in multiple adult tissues (subcutaneous adipose, visceral adipose, adrenal gland, aorta, coronary artery, tibial artery, brain, mammary tissue, transverse colon, oesophagus mucosa, oesophagus muscularis, transformed fibroblasts, atrial appendage, left ventricle, liver, lung, skeletal muscle, tibial nerve, ovary, pancreas, prostate, pituitary, not sun exposed skin, sun exposed skin, stomach, testis, thyroid, uterus, vagina and whole blood).

Category: Imprinted genes

Links: Gene   OMIM    Record:211 Last Modified 8/3/2017

Taxon: Human

Chromosome: 14

Location: 14q32.31

Gene: MEG8 (SNORD112, SNORD113, SNORD114)

Description: Morcos L et al, (2011) showed allelic expression bias in fibroblast cell lines. Exclusive paternal expression was then shown in eight informative parent-offspring trios.
A complex transcription unit including MEG8 (orthologous to mouse Rian, and sheep Meg8) is host to three types of snoRNAs (SNORD112 [14q(0)], SNORD113 [14q(I)] and SNORD114 [14q(II)]). In mouse the orthologous snoRNAs, and Rian are maternally expressed, as is Meg8 in sheep (Cavaille J et al, 2002).
Baran Y et al (2015) found evidence of imprinting of MEG8 (using RNA-seq) in adult adrenal gland, brain, ovary and pituitary tissues. Allelic expression of MEG8 in other tissues was also consistent with imprinting (subcutaneous adipose, transformed fibroblasts, atrial appendage, pancreas, testis, uterus and vagina).

Category: Imprinted genes

Links: Gene   Record:390 Last Modified 8/3/2017

Taxon: Human

Chromosome: 14

Location: 14q32.31, 101.1 Mb (Mar 06)

Gene: DIO3 (provisional data)

Description: In human neonatal foreskin DIO3 (deiodinase, iodothyronine, type III) showed biased allelic expression with an average imbalance of 74:36. In two cases the more highly expressed allele was paternally derived. However, in one adult skin sample the materally derived allele was more highly expressed. It was suggested that the different parent-of-origin is attributable to different promoter usage (Martinez ME et al, 2016).
In placenta, protein expression and quantitative real-time PCR showed that DIO3 expression was similar between three patients with paternal UPD14 and controls, arguing against imprinting (Kagami M et al, 2012).
Ogata T & Kagami M (2015) argue that absence of hypothyroidism in Kagami-Ogata syndrome and hyperthyroidism in Temple syndrome (imprinting disorders) indicates that DIO3 isn’t an imprinted gene, as DIO3 acts as an inactivator of thyroid hormones.

The mouse homologue of DIO3 is imprinted (Hernandez A et al, 2002).
Comment: More data are needed (both number of informative samples, and evidence of different promoter usage).

Category: Other

Links: Gene   Record:395 Last Modified 2/14/2017

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