Imprinted
genes in Humans
Species: Human
Chromosome: 01 Location: 1p36.33
Gene: p73
Description: p73 was
reported to be maternally expressed (Kaghad M, Cell 1997;90:809-819) and located in the region showing preferential
maternal loss of heterozygosity in
neuroblastomas without N-MYC amplification (Caron H, Hum.Mol.Genet. 1995;4:535-9). In contrast no imprinting of p73
was found in 27 of 29 lung specimens
and in one case with allelic imbalance the expressed was paternally derived (Nomoto S, Can.Res.
1998;58:1380-83). Evidence Type:
Expression data Last Modified: 2/12/98
Species: Human
Chromosome: 01 Location:
Gene:
Description: Maternal
UPD (1 case, Field LL, Am.J.Hum.Genet. 1998;63:1216-20) and maternal heterodisomy including partial isodisomy
of 1q (Pulkkinen L, Am.J.Hum.Genet.
1997;61:611-619) have been reported. No abnormal phenotype was detected. One case of paternal UPD resulted
in the recessive skeletal dysplasia,
pycnodysostosis, but the phenotype was otherwise normal, suggesting an
absence of paternally repressed genes
(Gelb BD, Am.J.Hum.Genet. 1998;62:848-54). Evidence Type: Disomy (UPD) Last
Modified: 2/12/98
Species: Human
Chromosome: 01 Location: 1p36
Gene: L211
Description: Clone
L211 is a differentially methylated sequence in human 1p36 near p73 (Landers M, Am.J.Hum.Genet.
1998;63(4 suppl):A22). Evidence Type: Miscellaneous Last Modified: 29/1/99
Species: Human
Chromosome: 02 Location: 2p24
Gene: N-MYC Description: In neuroblastoma
the paternal allele is preferentially amplified (Cheng JM, Nature 1993;4:191-194). Evidence Type: Miscellaneous
Last Modified: 22/10/98
Species: Human
Chromosome: 02 Location: Gene:
Description: Maternal UPD (5 cases) is possibly associated with an
abnormal phenotype (Shaffer LG,
Am.J.Hum.Genet. 1997;61:461-462). Evidence Type: Disomy (UPD) Last Modified:
22/10/98
Species: Human
Chromosome: 04 Location: 4q21-q22
Gene:
Description: Anomalous
imprinting has been hypothesised as the reason for the central nervous system overgrowth in the
4q21/4q23 syndrome (no direct evidence)
(Nowaczyk MJM, Am.J.Med.Genet. 1997;69:400-405). Evidence Type:
Miscellaneous Last Modified: 2/12/98
Species: Human
Chromosome: 04 Location:
Gene:
Description: Maternal
UPD (1 case) has been reported. Apart from infertility, the phenotype was normal and imprinting was
considered unlikely (Ledbetter DH,
Hum.Mol.Genet. 1995;4:1757-1764). Evidence Type: Disomy (UPD) Last
Modified: 22/10/98
Species: Human
Chromosome: 04 Location: 4p16.3
Gene: "Wolf-Hirschhorn
Syndrome"
Description:
Preferential paternal origin of the 4p16 deletion has been reported (Tupler R, J.Med.Genet. 1992;29:53-55;
Quarrell OWJ, J.Med.Genet.
1991;28:256-9), but a few cases of maternal deletion have been reported
(see OMIM #194190). Evidence Type: Miscellaneous Last Modified:
12/11/98
Species: Human
Chromosome: 05 Location: 5q23-q31
Gene: U2AFBPL
Description: U2AFBPL
is the human homologue of U2af1-rs1 (see mouse 11) which is imprinted in mice but U2AFBPL is not
imprinted in human placenta (Pearsall RS,
Biochem.Biophys. Res. Comm. 1996;222:171-7). Evidence Type: Expression
data Last Modified: 22/10/98
Species: Human
Chromosome: 05 Location:
Gene:
Description: Paternal
UPD (1 case) has been reported but imprinting is unlikely (Ledbetter DH, Hum.Mol.Genet.
1995;4:1757-1764). Evidence Type: Disomy (UPD) Last Modified: 22/10/98
Species: Human
Chromosome: 06 Location: 6q25.3-q26
Gene: MAS1
Description: MAS1 (a
tyrosine kinase protooncogene) showed monoallelic expression in human breast (parent-of-origin not determined,
Miller N, Genomics 1997;46:509-12), but
was reported to be not imprinted in human fetuses (Riesewijk AM, Genomics 1996;35:380-382). Evidence Type: Expression
data Last Modified: 24/11/98
Species: Human
Chromosome: 06 Location: 6q25.3
Gene: IGF2R, M6PR
Description: IGF2R
(Insulin-like growth factor II receptor; mannose 6-phosphate receptor, cation independent) is maternally
expressed in mouse but there are
conflicting data from humans. It may be polymorphically imprinted in
humans. Allele specific methylation
(methylation of the active maternal allele) is
maintained in humans (Barlow DP, Nature 1991;349:84-87; Kalscheuer
VM, Nat.Genet. 1993;5:74-78;
Polychronakos C, Current Directions in Insulin-Like Growth Factor Research 1994;189-203; Xu Y,
Biochem.Biophys.Res.Comm.
1993;197:747-754; Smrzka OW, Hum.Mol.Genet. 1995;4:1945-1952; Stöger R,
Cell 1993;73:61-71; Riesewijk AM,
Genomics 1996;31:158-166). Evidence Type: Expression data Last Modified:
29/10/98
Species: Human
Chromosome: 06 Location: 6q22-23
Gene: "Neonatal diabetes"
Description: Neonatal
diabetes mellitus. Several cases of neonatal diabetes had paternal UPD 6 (Temple IK, Nat.Genet.
1995;9:110-112; Gardner RJ,
Am.J.Hum.Genet. 1998;63(4 suppl):A55). Additionally, paternal UPD was
associated with agenesis of pancreatic
beta cells and neonatal diabetes (Abramowicz MJ, J.Clin.Invest. 1994;94:418-421) although paternal UPD has also
occurred in a normal child (Welch TR,
J.Clin.Invest. 1990;86:675-678). The critical region may be 6q22-q23: two cases showed duplication
6q22-q23; one family showed linkage
(Robinson DO, Am.J.Hum.Genet. 1997;61(Suppl.):A38; Temple IK,
Hum.Mol.Genet. 1996;5:1117-1121; Arthur
EI, Eur.J.Hum.Genet. 1997;5:417-419). Analysis of another paternal duplication mapped the breakpoints to 6q24.3 and
6q24.1 (Gardner RJ, Am.J.Hum.Genet.
1998;63(4 suppl):A55). The cases involving
duplication suggest that gain of function of a paternally expressed gene
is the mechanism of disease. Evidence
Type: Disomy (UPD) Last Modified: 1/2/99
Species: Human
Chromosome: 06 Location:
Gene:
Description: UPD 6 has
rarely been reported despite numerous studies of families at the HLA locus. Maternal UPD was detected
in a developmentally normal patient
(van den Berg-Loonen EM, Hum.Immunol. 1996;45:46-51). Paternal UPD is
discussed in the 6q entry on neonatal
diabetes. Evidence Type: Disomy (UPD) Last Modified: 22/10/98
Species: Human
Chromosome: 06 Location:
Gene: clone L59
Description: Clone 59
is from a differentially methylated region on human 6 (Landers M, Am.J.Hum.Genet. 1998;63(4 suppl):A22). Evidence Type:
Miscellaneous Last Modified: 29/1/99
Species: Human
Chromosome: 07 Location: 7p11.2-p12
Gene: GRB10
Description: GRB10
(Growth factor receptor-bound protein 10) is maternally expressed in mice (Miyoshi N,
Proc.Natl.Acad.Sci.USA 1998;95:1102-7) but no
human data has been reported (see mouse 7). Evidence Type: Miscellaneous
Last Modified: 22/10/98
Species: Human
Chromosome: 07 Location: 7q11.23
Gene:
Description: Williams
syndrome was associated with significantly more severe growth retardation and microcephaly if the
associated deletion of 7q11.23 was
maternally derived (Perez Jurado LA, Am.J.Hum.Genet. 1996;59:781-92).
Evidence Type: Inheritance pattern Last Modified: 22/10/98
Species: Human
Chromosome: 07 Location: 7q32
Gene: MEST, PEG1
Description: MEST
(Mesoderm-specific transcript / Paternally expressed gene 1, member of the alpha/beta hydroxylase fold
family) is paternally expressed in
human fetal tissues, but biallelically expressed in adult blood
(Kobayashi S, Hum.Mol.Genet.
1997;6:781-6; Riesewijk AM, Genomics 1997;42:236-244). Peg1 is imprinted in mice (Kaneko-Ishino T, Nat.
Genet. 1995;11:52-59). Evidence Type: Expression data Last Modified: 29/10/98
Species: Human
Chromosome: 07 Location:
Gene:
Description: Several
cases of maternal iso- and hetero-disomy in Russell-Silver syndrome indicate the presence of imprinted
growth gene(s) (Kotzot D,
Hum.Mol.Genet. 1995;4:583-587; Langlois S, J.Med.Genet.
1995;32:871-875). Multiple genes on
chromosome 7 show parent-of-origin dependent methylation (details not reported: Hannula K,
Am.J.Hum.Genet. 1998;63(4 Suppl):A328).
Evidence Type: Disomy (UPD) Last Modified: 1/2/99
Species: Human
Chromosome: 08 Location:
Gene:
Description: Paternal
UPD is associated with normal development (Benlian P, Am.J.Hum.Genet. 1996;59:431-436). Evidence Type: Disomy (UPD)
Last Modified: 22/10/98
Species: Human
Chromosome: 09 Location: 9q34
Gene:
Description: Loss of
maternal ABO antigens has been reported in 4/4 acute
myeloid leukaemia
cases (Dobrovic A, Blood 1993;82:1684-1685).
Evidence Type:
Miscellaneous
Last Modified:
27/10/98
Species: Human
Chromosome: 09 Location:
Gene: Description: Maternal UPD (4 cases)
has been reported but parent-of-origin
effects were considered unlikely (Ledbetter DH, Hum.Mol.Genet.
1995;4:1757-1764; Hurst LD, Trends
Genet.1997;13:436-443). Evidence Type: Disomy (UPD) Last Modified: 24/11/98
Species: Human
Chromosome: 09 Location: 9p22-pter
Gene:
Description: Deletion
of the paternally derived chromosome 9 (p22-pter) was associated with minimal dysmorphic stigmata (usually 9p deletion
is associated with distinctive
features). The authors hypothesise that imprinting may influence the phenotype (Kleczkowska A,
Genet.Counselling 1992;3(1):49-52).
Evidence Type: Inheritance pattern Last Modified: 1/2/99
Species: Human
Chromosome: 10 Location:
Gene:
Description: Maternal
UPD (2 cases) has been reported, but parent-of-origin effects were considered unlikely (Ledbetter DH, Hum.Mol.Genet.
1995;4:1757-1764; Hurst LD, Trends
Genet.1997;13:436-443). Evidence Type: Disomy (UPD) Last Modified: 22/10/98
Species: Human
Chromosome: 11 Location: 11p15.5
Gene: BWS
Description: Imprinted
gene(s) in the 11p15 cluster are involved in the Beckwith Wiedemann syndrome. Duplication of the
active paternal copy of IGF2 is a leading
candidate mechanism for this syndrome (Morison IM, Mole.Med.Today 1998;4:110-15). Evidence Type: Miscellaneous
Last Modified: 29/10/98
Species: Human
Chromosome: 11 Location: 11p15.5
Gene: H19
Description: H19 is
maternally expressed in mouse and humans. The gene product is an abundant untranslated RNA of unknown
function (Barlow DP, Nature
1991;349:84-87; Rachmilewitz J, FEBS Lett. 1992;309:25-28; Leighton PA,
Nature 1995;375:34-39; Rainier S,
Nature 1993;362:747-749; Zhang Y, Nat.Genet.
1992;1:40-44). Evidence Type: Expression data Last Modified: 27/10/98
Species: Human
Chromosome: 11 Location: 11p15.5
Gene: IGF2, Insulin-like growth factor 2,
IGF-II
Description: IGF2
(Insulin-like growth factor 2, a fetal growth factor) is paternally expressed in humans and rodents.
Expression is not imprinted in the
choroid plexus, leptomeninges, brain, adult human liver and
chondrocytes. It is probably
"secondarily imprinted" under the control of the H19 locus (Rainier
S, Nature 1993;362:747-749; DeChiara
TM, Cell 1991;64:849-859; Ogawa O, Nature
1993;362:749-751; Ohlsson R, Nat.Genet. 1993;4:94-97). Evidence Type:
Expression data Last Modified: 2/12/98
Species: Human
Chromosome: 11 Location: 11p15.5
Gene: INS, insulin
Description: INS is
paternally expressed in mouse yolk sac (Giddings SJ, Nat.Genet. 1994;6:310-312), but not imprinted in human or mouse
pancreas (Giddings SJ, Nat.Genet. 1994;6:310-312;
Bennett ST, Nat.Genet. 1995;9:284-92).
Insulin is suspected to be imprinted in humans since the susceptibility
to Type 1 diabetes may be influenced by
the parent-of-origin of insulin alleles, but the mechanism of this effect is unclear (Bennett ST, J.Autoimmun.
1996;9:415-421; Bennett ST,
Annu.Rev.Genet. 1996;30:343-370; Bennett ST, Nat.Genet. 1997;17:350-352; Polychronakos C, Dev.Genet.
1995;17:253-262, Margaritte-Jeannin P,
Am.J.Hum.Genet. 1995;56:1080-87). Evidence Type: Inheritance pattern Last
Modified: 24/11/98
Species: Human
Chromosome: 11 Location: 11p15.5
Gene: ASCL2, HASH2
Description: ASCL2
(Achaete Scute complex like 2, the human homologue of murine Mash2, a helix-loop-helix transcription
factor) is maternally expressed. It is
expressed in human extravillous trophoblasts (Alders M,
Hum.Mol.Genet. 1997;6:859-867) and in
the spongiotrophoblast cells of mouse placenta (Guillemot F, Nat.Genet. 1995;9:235-242; Guillemot F,
Nature 1994;371:333-336). Evidence Type: Expression data Last Modified:
27/10/98
Species: Human
Chromosome: 11 Location: 11p15.5
Gene: TAPA1
Description: TAPA1.
Preliminary data suggest imprinting in the mouse (see mouse 7). Evidence Type: Last Modified: 13/10/98
Species: Human
Chromosome: 11 Location: 11p15.5
Gene: KCNA9, KvLQT1
Description: KvLQT1
(potassium channel involved in long QT syndrome) is maternally expressed in humans and in mouse embryos. Its
expression is imprinted in several
tissues but not in the heart (Lee MP, Nat.Genet. 1997;15:181-185). A paternally-expressed antisense transcript
has been reported (Higgins MJ,
Am.J.Hum.Genet. 1998;63(4 Suppl):A328). Evidence Type: Expression data
Last Modified: 1/2/99
Species: Human
Chromosome: 11 Location: 11p15.5
Gene: CDKN1C, p57KIP2
Description: CDKN1C (a
cyclin-dependent kinase inhibitor) is maternally expressed in humans and mouse. It is completely imprinted in
mouse but only partially in humans
(Hatada I, Nat.Genet. 1995;11:204-206; Matsuoka S, Proc.Natl.Acad.Sci.USA 1996;93:3026-3030; Taniguchi T,
Oncogene 1997;14:1201-1206; Chung WY,
Hum.Mol.Genet. 1996;5:1101-1108). Evidence Type: Expression data Last Modified:
27/10/98
Species: Human
Chromosome: 11 Location: 11p15.5
Gene: 2G3-8
Description: 2G3-8 is
under study, but may show allelic expression bias in some tissues (Dao D, Hum.Mol.Genet.
1998;7:597-608). Evidence Type: Expression data Last Modified: 27/10/98
Species: Human
Chromosome: 11 Location: 11p15.5
Gene: IMPT1, BWR1A, ORCTL2
Description: IMPT1
(Imprinted Multi-membrane-spanning Polyspecific Transporter-like gene-1) is relatively repressed on the paternal
allele (Dao D, Hum.Mol.Genet.
1998;7:597-608; Schwienbacher C, Proc.Natl.Acad.Sci.USA 1998;95:3873-3878; Cooper PR, Genomics
1998;49:38-51). Evidence Type: Expression data Last Modified: 27/10/98
Species: Human
Chromosome: 11 Location: 11p15.5
Gene: IPL, TSSC3, BWR1C
Description: IPL
(Imprinted in Placenta and Liver, Tumor-Suppressing STF cDNA 3) shows maternal expression with relative
repression of the paternal allele. It is
expressed in placenta and most fetal tissues and is homologous to
mouse apoptosis promoting gene TDAG51
(Schwienbacher C, Proc.Natl.Acad.Sci.USA
1998;95:3873-3878; Lee MP, Can.Res. 1998;58:1052-1056; Qian N, Hum.Mol.Genet. 1997;6:2021-2029). Evidence Type: Expression
data Last Modified: 27/10/98
Species: Human
Chromosome: 11 Location: 11p13
Gene: WT1
Description: WT1
(Wilms tumour 1, a zinc finger protein). There are conflicting data. It was reported to be partially or
completely imprinted and maternally
expressed in some tissues (placenta and brain) but was paternally
expressed in fibroblasts and
lymphocytes from some individuals (Jinno Y, Nat Genet. 1994;6:305-309; Mitsuya K, Hum.Mol.Genet.
1997;6:2243-2246). De novo germ line
mutations of WT1 preferentially occur during male gametogenesis (Huff
V, Am.J.Hum.Genet. 1990;47:155-160).
Evidence Type: Expression data Last Modified: 29/10/98
Species: Human
Chromosome: 11 Location: 11q13
Gene: FCERIB
Description: FCERIB
(beta subunit of the high-affinity IgE receptor). In allergic asthmatics the Leu181 allele was always maternally
inherited (10/10 families) (Shirakawa
T, Nat.Genet. 1994;7:125-129). Evidence Type: Inheritance pattern Last
Modified: 27/10/98
Species: Human
Chromosome: 11 Location: 11q13.1 and 11q22.3-q23.3
Gene:
Description: Familial
glomus tumours (nonchromaffin paragangliomas). Linkage studies suggest two distinct loci but the
tumour susceptibility is always
inherited from carrier fathers (Baysal BE, Am.J.Hum.Genet.
1997;60:121-132; Mariman ECM,
Hum.Genet. 1995;95:56-62; van der Mey AGL, Lancet 1989;2:1291-1294; Milunsky J, Am.J.Med.Genet. 1997;72:66-70).
Evidence Type: Inheritance pattern Last Modified: 29/10/98
Species: Human
Chromosome: 11 Location:
Gene:
Description: Paternal
UPD is one of the causative chromosomal events associated with Beckwith-Wiedemann syndrome. See
individual entries for 11p. BWS associated
UPD is usually partial in that it involves only a portion of 11p (this
always includes 11p15.5), and it is
always mosaic; that is, affected individuals always show a mixture of normal cells (biparental disomy) and UPD
cells. Evidence Type: Disomy (UPD) Last
Modified: 12/11/98
Species: Human
Chromosome: 11 Location: 11p15
Gene: ZNF214
Description: ZNF214 is
a novel imprinted zinc finger gene within the BWSCR2 region of 11p15 (Alders M, Am.J.Hum.Genet. 1998;63(4
suppl):A319). Evidence Type: Expression
data Last Modified: 1/2/99
Species: Human
Chromosome: 11 Location: 11p15
Gene: ZNF215
Description: ZNF215 is
a novel imprinted zinc finger gene within the BWSCR2 region of 11p15 (Alders M, Am.J.Hum.Genet. 1998;63(4
suppl):A319). Evidence Type: Expression
data Last Modified: 29/1/99
Species: Human
Chromosome: 13 Location: 13q14
Gene: RB locus
Description: The
retinoblastoma gene itself does not appear to be imprinted but there may be parent-of-origin effects on the
transmission of retinoblastoma
susceptibility in humans (Naumova A, Am.J.Hum.Genet. 1994;54:264-273)
and in mice (earlier onset of tumours
when mutant Rb is paternally inherited) (Nikitin AY, Cancer Res.1997;57:4274-8). In an unexplained observation,
the parental origin of a chromosomal
rearrangement near RB affected the NruI restriction enzyme digestion pattern (Blanquet V, Genomics 1991;10:350-5). De
novo mutations of RB preferentially
occur during male gametogenesis - this is not usually regarded as an imprinting effect (Toguchida J, Nature
1989;338:156-8; Kato MV, Hum.Genet.
1994;94:31-8). Evidence Type: Inheritance pattern Last Modified: 24/11/98
Species: Human
Chromosome: 13 Location: 13q14
Gene: HTR2a
Description: HTR2a
(serotonin (hydroxytryptamine) receptor type 2a) was biallelically expressed in normal tissues, but in fibroblasts of
retinoblastoma patients with germ line
deletions or translocations it was only expressed in those with a paternally derived deletion or translocation (5/5),
but not in those with a maternal
deletion (2/2). Promoter region methylation (partial) corresponded positively with expression (Kato MV,
Am.J.Hum.Genet. 1996;59:1084-1090). It
is imprinted in mouse (see mouse 14). Evidence Type: Expression data Last
Modified: 27/10/98
Species: Human
Chromosome: 13 Location:
Gene:
Description: Maternal
(3 cases) and paternal UPD (1 case) have been reported but parent-of-origin effects were considered
unlikely (Ledbetter DH, Hum.Mol.Genet.
1995;4:1757-1764). Evidence Type: Disomy (UPD) Last Modified: 29/10/98
Species: Human
Chromosome: 14 Location: 14q24.3-q31
Gene:
Description: A case
report of dup(14q24.3-31), inherited from a phenotypically normal father, suggests that this region may
be imprinted (Robin NH, Am.J.Med.Genet.
1997;71:361-365). Evidence Type: Miscellaneous Last Modified: 27/10/98
Species: Human
Chromosome: 14 Location:
Gene:
Description: Both
paternal and maternal UPD suggest parent-of-origin effects on chromosome 14. Maternal heterodisomy and
isodisomy (8 cases in literature) is
associated with a characteristic phenotype (hypotonia, motor
developmental delay, mild dysmorphic
facial features, low birth weight, growth abnormalities (precocious puberty)) (Ledbetter DH,
Hum.Mol.Genet. 1995;4:1757-1764; Hurst LD,
Trends Genet.1997;13:436-443; Tomkins DJ, Eur.J.Hum.Genet.
1996;4:153-159). Paternal UPD (4 cases)
is associated with severe mental and musculoskeletal phenotype (Walter CA, Am.J.Med.Genet. 1996;65:259-265; Cotter
PD, Am.J.Med.Genet. 1997;70:74-79).
Evidence Type: Disomy (UPD) Last Modified: 29/10/98
Species: Human
Chromosome: 15 Location: 15q11-q13
Gene:
Description: The
15q11-q13 region contains a cluster of imprinted genes that may be involved in the pathogenesis of the
Prader-Willi and Angelman syndromes
(Glenn CC, Mol.Hum.Reprod. 1997;3:321-332). See individual entries.
Evidence Type: Miscellaneous Last Modified: 27/10/98
Species: Human
Chromosome: 15 Location: 15q11-q13
Gene: ZNF127, FNZ127
Description: ZNF127
and FNZ127 are two overlapping paternally expressed transcripts. ZNF127 putatively encodes a 505 amino acid
polypeptide-containing zinc-finger
motif (Glenn CC, Mol.Hum.Reprod. 1997;3:321-332; Glenn CC, Hum.Mol.Genet. 1993;2:1377-1382; Driscoll
DJ, Genomics 1992;13:917-24). Evidence Type: Expression data Last Modified:
27/10/98
Species: Human
Chromosome: 15 Location: 15q11-q13
Gene: NDN, Necdin
Description: NDN is
paternally expressed in brain (human and mouse) and fibroblasts. It is expressed in differentiated neurones
(MacDonald HR, Hum.Mol.Genet.
1997;6:1873-1878; Jay P, Nat.Genet. 1997;17:357-361; Watrin F, Eur.J.Hum.Genet. 1997;5:324-332). Evidence
Type: Expression data Last Modified: 27/10/98
Species: Human
Chromosome: 15 Location: 15q11-q13
Gene: BD exons of SNRPN
Description: BD exons
of SNRPN. This region may constitute the 15q imprinting centre and is comprised of alternate 5'
exons (the BD exons, BD1D, BD1C, BD1B,
BD1B*, BD1A, BD2, BD3, BD4) of SNRPN. Deletions of these exons cause
Angelman syndrome perhaps through
failure to erase the imprint from the previous
generation (Dittrich B, Nat Genet. 1996;14:163-170; Ning Y, Genome
Res. 1996;6:742-746; Saitoh S,
Proc.Natl.Acad.Sci.USA 1996;93:7811-7815; Faerber C, Am.J.Hum.Genet. 1998;63(4 suppl)A54). Evidence Type: Inheritance
pattern Last Modified: 1/2/99
Species: Human
Chromosome: 15 Location: 15q11-q13
Gene: SNRPN
Description: SNRPN
(small nuclear ribonucleoprotein-associated polypeptide N) is paternally expressed and may be involved in
the pathogenesis of Prader-Willi
syndrome. It may be secondarily imprinted, under the control of an
imprinting centre (Glenn CC,
Hum.Mol.Genet. 1993;2:2001-2005; Sutcliffe JS, Nat.Genet. 1994;8:52-58). Evidence Type: Expression data
Last Modified: 27/10/98
Species: Human
Chromosome: 15 Location: 15q11-q13
Gene: PAR-SN
Description: PAR-SN
(an RNA transcript between SNRPN and PAR5) is paternally expressed in lymphoblasts (Ning Y, Genome
Res. 1996;6:742-746). Evidence Type: Expression data Last Modified: 27/10/98
Species: Human
Chromosome: 15 Location: 15q11-q13
Gene: PAR5, D15S226E
Description: PAR5
(Prader Willi Angelman Region 5) is a paternally expressed transcript which contains no open reading
frames (Sutcliffe JS, Nat.Genet.
1994;8:52-58). Evidence Type: Expression data Last Modified: 27/10/98
Species: Human
Chromosome: 15 Location: 15q11-q13
Gene: IPW
Description: IPW
(Imprinted in Prader-Willi) is paternally expressed but probably untranslated (Wevrick R,
Hum.Mol.Genet. 1994;3:1877-1882). Evidence Type: Expression data Last Modified:
27/10/98
Species: Human
Chromosome: 15 Location: 15q11-q13
Gene: PAR1, D15S227E
Description: PAR1
(Prader Willi Angelman Region 1) is paternally expressed but probably contains no open reading frames
(Sutcliffe JS, Nat.Genet.
1994;8:52-58). Evidence Type: Expression data Last Modified: 27/10/98
Species: Human
Chromosome: 15 Location: 15q11-q13
Gene: UBE3A, E6-AP, ubiquitin protein
ligase 3A
Description: UBE3A 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, Nat.Genet.
1997;17:14-15; Vu TH, Nat.Genet. 1997;17:12-13). UBE3A has a downstream transcript which shows predominant
maternal expression and an antisense
transcript which is expressed exclusively from the paternal allele (Rougeulle C, Nat.Genet.
1998;19:15-16). Evidence Type:
Expression data Last Modified: 12/11/98
Species: Human
Chromosome: 15 Location: 15q11-q13
Gene: GABAA receptor subunit genes,
GABRB3, GABRA5, GABRG3
Description: The GABAA
receptor subunit genes were reported to be paternally expressed (Meguro M, Hum.Mol.Genet. 1997;6:2127-33), but there is
conflicting evidence (see Jiang Y,
Curr.Opin.Genet.Devel. 1998;8:334-42). There is paternal methylation of the 5' end of GABRB3 (Meguro
M). Evidence Type: Expression data Last
Modified: 24/11/98
Species: Human
Chromosome: 15 Location: 15q11-q13
Gene:
Description: Autism.
In a family, autism was associated with a 15q11-q13 duplication only when maternally transmitted (Cook EH, Jr,
Am.J.Hum.Genet. 1997;60:928-934).
Evidence Type: Inheritance pattern Last Modified: 27/10/98
Species: Human
Chromosome: 16 Location:
Gene:
Description: Maternal
UPD (9 cases) has been reported but most had trisomy 16 mosaicism, to which growth retardation could
be attributed. Imprinting was
considered possible based on studies of 26 patients with placental
mosaicism for trisomy 16 (Robinson WP,
Am.J.Hum.Genet. 1997;60:917-927) and based on
developmental anomalies in a minority of patients (anal atresia,
and hypospadius) (Ledbetter DH,
Hum.Mol.Genet. 1995;4:1757-1764). Paternal UPD (1 case) has been reported but parent-of-origin effects were
considered unlikely (Ledbetter DH,
Hum.Mol.Genet. 1995;4:1757-1764). Evidence Type: Disomy (UPD) Last Modified:
29/10/98
Species: Human
Chromosome: 18 Location: 18q11
Gene: Clone L3
Description: Clone L3
is a differentially methylated sequence in human 18q11, a region homologous to the murine region
containing Impact (Landers M,
Am.J.Hum.Genet. 1998;63(4 suppl):A22).
Evidence Type: Miscellaneous Last Modified: 29/1/99
Species: Human
Chromosome: 19 Location: 19q13.4
Gene: PEG3
Description: PEG3, the
human homologue of imprinted mouse gene Peg3 (Kim J, Genome Res. 1997;7:532-540) (see mouse 7) is located here, but
its imprinting status has not been not
reported. Evidence Type: Last Modified:
27/10/98
Species: Human
Chromosome: 20 Location: 20q13.11
Gene: GNAS1, Gs alpha, NESP55, XL alpha s
Description:
Imprinting depends on the promoter usage. The most 5' promoter and exon encodes NESP55 which is expressed
exclusively from the maternal allele. The
XL alpha s exon which is 11 kb 3', is paternally expressed, while the Gs
alpha transcripts from exon 2 are
biallelically expressed (Hayward BE,
Proc.Natl.Acad.Sci.USA 1998;95:15475-15480). There is
maternal-specific methylation ~35 kb
upstream of exon 1 (Hayward BE, Proc.Natl.Acad.Sci.USA 1998;95:10038-43). The previously reported
inheritance pattern of Albright's
hereditary osteodystrophy suggested imprinting of GNAS1. 33/36
transmitting parents were maternal and
all 60 maternal offspring had full expression of the phenotype (pseudo-hypoparathyroidism type Ia) whereas all 6
paternal offspring had partial
expression (pseudopseudo-hypoparathyroidism) (Davies SJ, J. Med. Genet. 1993;30:101-103). See also mouse Gnas
which shows paternal repression in
renal cortex. Evidence Type: Expression data Last Modified: 1/2/99
Species: Human
Chromosome: 21 Location:
Gene:
Description: Maternal
(3 cases) and paternal UPD (2 cases) have been reported but parent-of-origin effects were considered
unlikely (Ledbetter DH, Hum.Mol.Genet.
1995;4:1757-1764). Evidence Type: Disomy (UPD) Last Modified: 29/10/98
Species: Human
Chromosome: 22 Location:
Gene:
Description: Maternal
(3 cases) and paternal UPD (1 case) have been reported but parent-of-origin effects were considered
unlikely (Ledbetter DH, Hum.Mol.Genet.
1995;4:1757-1764; Schinzel AA, Am.J.Hum.Genet. 1994;54:21-24). Evidence
Type: Disomy (UPD) Last Modified: 29/10/98
Species: Human
Chromosome: 22 Location: 22q11
Gene: clone L88
Description: Clone L88
is a differentially methylated sequence in the DiGeorge syndrome region on human 22q11 (Landers M,
Am.J.Hum.Genet. 1998;63(4 suppl):A22).
Evidence Type: Miscellaneous Last Modified: 29/1/99
Species: Human
Chromosome: X Location: Xq13.2
Gene: XIST
Description: XIST
shows preferential paternal expression with associated silencing of the paternal X chromosome in
the extraembryonic tissues of mouse and
in trophoblastic cells in humans (Goto T, Mole.Hum.Reprod. 1997;3:77-80; Takagi N, Nature 1975;256:640-642). XIST is
an untranslated RNA. Most genes on the
X chromosome could be described as "secondarily imprinted" in
response to XIST-induced silencing
(Brown CJ, Nature 1991;349:38-44; Kay GF, Cell
1994;77:639-650). Evidence Type: Expression data Last Modified: 24/11/98
Species: Human
Chromosome: X Location: Xp11.23-qter
Gene: Unknown
Description: Turner
syndrome patients with a maternally retained X (45,Xm) showed significantly poorer verbal and
higher-order executive function skills
than those with 45,Xp (Skuse DH, Nature 1997;387:705-708). A higher
prevalence of cardiovascular
abnormalities and neck webbing has been noted when the retained X was maternal (Chu CE,
J.Med.Genet. 1994;31:840-842). Evidence Type: Inheritance pattern Last
Modified: 27/10/98
Species: Human
Chromosome: X Location:
Gene:
Description: Maternal
UPD had obvious clinical stigmata (Quan F, Am.J.Hum.Genet. 1997;60:160-165). Paternal UPD (1 case) was
associated with impaired gonadal
function and shortness of stature (Schinzel AA, Hum.Genet. 1993;92:175-8).
Evidence Type: Disomy (UPD) Last Modified: 29/10/98
Species: Human
Chromosome: Unknown Location:
Gene: RET or other modifier gene
Description: Familial
Hirschsprung disease. Affected patients with familial Hirschsprung disease were more likely to inherit the mutant RET
protooncogene (10q11.2) from their
mothers (Peretz H, Hum.Mutation 1997;10:155-159). Evidence Type: Inheritance
pattern Last Modified: 29/10/98
Species: Human
Chromosome: Unknown Location:
Gene: NF2 or other modifier gene
Description:
Neurofibromatosis Type 2 shows earlier onset and more severe disease when maternally inherited. NF2 is
caused by mutations of SCH/Merlin on
22q12 (Evans DGR, J.Med.Genet. 1992;29:841-846; Miller M, Lancet 1978;I:1071-1073). Evidence Type:
Inheritance pattern Last Modified: 29/10/98
Species: Human
Chromosome: Unknown Location:
Gene: "Schizophrenia"
Description: Negative
symptom scores and clinical course scores were
significantly higher (worse) when paternally inherited, but there is
also evidence for anticipation suggesting
the involvement of an unstable
trinucleotide repeat (Ohara K, Biol.Psych. 1997;42:760-766; O'Donovan
MC, Nat.Genet. 1995;10:380-381; Valero
J, Acta.Psych.Scand. 1998;97:343-50, Bassett
AS, Hum.Genet. 1994;54:864-70). Husted found that anticipation was
greater with paternal than with
maternal transmission (Husted J Am.J.Med.Genet. 1998;81:156-162). In contrast others have found no evidence of
true anticipation or parental affect on
age of onset (Asherson P, Brit.J.Psych. 1994;164:619-624). Affected sibling pairs were more likely to
be of the same sex when the history of
schizophrenia was on the paternal side (Crow TJ, Brit.J.Psych. 1989;155:92-7). Evidence Type: Inheritance
pattern Last Modified: 24/11/98
Species: Human
Chromosome: Unknown Location:
Gene: "Bipolar disorder"
Description: Bipolar
affective disorder. Cases with paternal transmission showed earlier onset, and anticipation was found
only with paternal inheritance. This
effect may be attributable to trinucleotide repeat expansions (O'Donovan
MC, Nat Genet. 1995;10:380-381; Oruc L,
Am.J.Hum.Genet. 1997;60:730-732;
Grigoroiu-Serbanescu M, Romanian J.Neurol.Psych. 1993;31:3-10; Grigoroiu-Serbanescu M, Acta Psych.Scand.
1995;92:365-370; Grigoroiu-Serbanescu
M, Brit.J.Psych. 1997;170:162-166; McMahon FJ, Am.J.Hum.Genet.
1995;56:1277-86; Stine OC,
Am.J.Hum.Genet. 1995;57:1384-1394). The presence of parental effects has been disputed by others (Kato T,
Am.J.Med.Genet. 1996;67:546-50). Evidence Type: Inheritance pattern Last
Modified: 29/10/98
Species: Human
Chromosome: Unknown Location:
Gene:
Description:
Progressive diaphyseal dysplasia (Engelmann disease). Imprinting and/or paternal-specific repeat expansion
has been proposed to explain phenotypic
variability and possible anticipation in a three generation family (Saraiva JM, Am.J.Med.Genet.
1997;71:348-352)." Evidence Type: Inheritance pattern Last Modified:
27/10/98
Species: Human
Chromosome: Unknown Location: ?3q21
Gene: "Brachmann-de Lange
syndrome"
Description:
Brachmann-de Lange syndrome. In all convincing autosomal dominant cases the transmitting parent was the
mother. This syndrome shows a variable
phenotype with growth retardation, facial dysmorphism including
micrognathia, microbrachycephaly, small
hands and feet, and mental retardation (de
Die-Smulders C, Clin.Genet. 1992;41:42-45). Evidence Type: Inheritance
pattern Last Modified: 29/10/98
Species: Human
Chromosome: Unknown Location:
Gene:
Description: Familial
hypertrophic cardiomyopathy. In a Mennonite kindred with dominant cardiomyopathy not linked to
beta-myosin heavy chain gene, a
disproportionate number of transmitting parents were females, ie, 2/32
(6%) offspring of males were affected
versus 7/12 (58%) offspring of females (Clarke
LA, Am.J.Hum.Genet. 1992;51(suppl.4):Abs 358). Evidence Type:
Inheritance pattern Last Modified: 27/10/98
Species: Human
Chromosome: Unknown Location:
Gene:
Description: Spina
bifida. In one series there were twice as many gene-carrying mothers as fathers (Chatkupt S,
Am.J.Med.Genet. 1992;44:508-512). Evidence Type: Inheritance pattern Last
Modified: 27/10/98
Species: Human
Chromosome: Unknown Location:
Gene:
Description: Psoriasis
vulgaris. Parental effect on birth weight has been reported. Also paternal inheritance caused more severe disease
(Traupe H, Am.J.Med.Genet.
1992;42:649-654). Evidence Type: Inheritance pattern Last Modified: 27/10/98
Species: Human
Chromosome: Unknown Location:
Gene:
Description: Tourette
syndrome showed parent-of-origin phenotype differences (Lichter DG, Neurol. 1995;45:924-928), and
maternally transmitted offspring showed
a significantly earlier age at onset (Eapen V, Neurol. 1997;48:934-937). These differences have not been confirmed by
others (Caron C, Neurol. 1997;49:637-638).
Evidence Type: Inheritance pattern Last Modified: 27/10/98
Species: Human
Chromosome: Unknown Location:
Gene:
Description:
Polycystic kidney disease. Predominant maternal transmission of PKD has been reported along with an earlier
onset of disease when maternally
inherited, but this was not confirmed by others (Torra R, Medicina
Clinica 1998;110:481-487; Zerres K,
Nephrol.Dialysis Transplant. 1995;10:7-9). Evidence Type: Inheritance pattern
Last Modified: 27/10/98
Species: Human Chromosome:
Unknown Location:
Gene:
Description: Crohn's
disease. Among 33 non-Jewish parent-child pairs with Crohn's disease 28 involved maternal transmission, whereas 5
involved paternal transmission (Akolkar
PN, Am.J.Gastro. 1997;92:2241-4). Evidence Type: Inheritance pattern Last
Modified: 27/10/98
Species: Human
Chromosome: Unknown Location:
Gene:
Description: Epilepsy.
A higher risk of seizures has been reported in the offspring of mothers than of fathers with epilepsy (Ottman R,
Am.J.Hum.Genet. 1988;43:257-64).
Evidence Type: Inheritance pattern Last Modified: 27/10/98
Species: Human
Chromosome: Unknown Location:
Gene: amyloid B precursor protein or a
modifier gene
Description:
Hereditary cerbral haemorrhage with amyloidosis-Dutch type has a higher mortality rate when paternally
transmitted (Bornebroek M, Brain,
1997;120:2243-9). HCHWA-D is an autosomal dominant disorder caused by a
single base change in the amyloid B
precursor protein gene on chromosome 21.
Evidence Type: Inheritance pattern Last Modified: 3/11/98
Species: Human
Chromosome: Unknown Location:
Gene: "Atrial septal defects"
Description: Offspring
of affected fathers were less likely to have ASD than offspring of affected mothers. Given that the disease penetrance
is lower in males than in females, a
bias in the opposite direction was expected (Rose V, J.Am.Coll.Cardiol. 1985;6:376-82). Evidence Type: Inheritance pattern Last Modified: 24/11/98
Species: Human
Chromosome: General Location:
Gene:
Description: In a
human parthenogenetic-normal chimera all blood cells were parthenogenetic (that is, maternally disomic
for all chromosomes), indicating that
paternal gene products are not required for haematopoiesis (Strain L, Nat.Genet. 1995;11:164). Evidence Type:
Disomy (UPD) Last Modified: 12/11/98
Species: Human
Chromosome: Location: 17q11.2
Gene: NF1
Description: De novo
mutations preferentially occur during male gametogenesis - this is not regarded as an imprinting effect
(Jadayel D, Nature 1990;343:558-9). In
contrast 4/4 de novo deletions occurred on the maternally-derived
chromosome (Ainsworth PJ, Hum.Mutat.
1997;9:452-457). Evidence Type:
Miscellaneous Last Modified: 2/12/98
Species: Human
Chromosome: Location: 10q11.2
Gene: RET
Description: De novo
mutations preferentially occur during male gametogenesis (25/25 cases)- this is not regarded as an
imprinting effect (Carlson KM,
Am.J.Hum.Genet. 1994;55:1076-82).
Evidence Type: Miscellaneous Last Modified: 24/11/98
Species: Human
Chromosome: Location: 22q11.2
Gene: DiGeorge syndrome
Description: Deletions
causing DiGeorge syndrome (Velo-cardio-facial syndrome) occur more frequently on the maternally
derived chromosome 22 (Seaver LH,
J.Med.Genet. 1994;31:830-4, Demczuk S, Hum.Genet. 1995;96:9-13).
Evidence Type: Miscellaneous Last Modified: 24/11/98