IVF九个印记基因

IVF九个印记基因 TP73 TP73(tumour protein p73)在血液和一些成神经瘤细胞系呈母源表达，(Kaghad M et al, 1997)。胎儿的胰腺和甲状腺、正常成人的肾脏和食管都已经证实存在母源表达(Mai M et al, 1998; Cai YC et al, 2000)。单等位基因表达于外周血再一次被证实(Martinez-Delgado et al, 2002)，3/4的胎儿脑组织中也有印记差异表达现象，其他的胎儿组织呈双表达(Hu JF et al, 2000)。27/29的肺组织样本中都不存在TP73印记差异表达现象，还有一例呈父源表达 (Nomoto S et al, 1998)。TP73是淋巴溜的候选肿瘤抑制基因(Martinez-Delgado et al, 2002)。 GNAS(20q13.2human ) GNAS1, Gs alpha, NESP55, XLalpha s, SANG (GNAS1-AS) Description: The GNAS1 gene contains three imprinted protein-coding transcripts, one non-coding transcript and one imprinted antisense transcript. 1. Gs-alpha (a small GTPases) is maternally expressed the pituitary gland (Hayward BE et al, 2001), thyroid and gonads (Mantovani G et al. 2002; Liu J et al, 2003; Germain-Lee EL et al, 2002), but is biallelically expressed in most other tissues (Hayward BE et al, Aug 1998). It is likely to be imprinted in the renal proximal tubules (Liu J et al, 2000). 2. XLalpha s (the extra-large variant of the G protein alpha-subunit) is paternally expressed (Hayward BE et al, Aug 1998). Multiple transcripts and protein isoforms are derived from the XL (XXL) promoter (Abramowitz J et al, 2004). 3. NESP55 (Neuroendocrine secretory protein 55, a chromogranin-like protein) is maternally expressed in multiple fetal tissues (Hayward BE et al, Dec 1998). 4. The exon 1A (exon A/B) transcript is probably not translated and is paternally expressed (Liu J et al, 2000). 5. SANG (GNAS1-AS) is a paternally expressed antisense transcript that spans the upstream NESP55 region (Hayward BE et al, 2000). The inheritance pattern of several diseases suggested imprinting of the GNAS1 gene . Albright hereditary osteodystrophy displays various physical abnormalities as well as end organ resistance to various hormones including parathyroid (pseudo-hypoparathyroidism type 1a) when inherited maternally (60 offspring from 33/36 maternal transmitting parents). However when this disease is transmitted paternally, offspring (6) suffer from the physical features of AHO but lack hormone resistance (pseudopseudo-hypoparathyroidism) (Davies SJ et al, 1993). Recent evidence that the Gs-alpha transcript is predominantly maternally expressed in the thyroid gland and gonads is consistent with this inheritance pattern (Mantovani G et al. 2002). Progressive osseous heteroplasia is attributable to paternally inherited mutations of GNAS1 (Shore EM et al, 2002). Abnormal imprinting (loss of methylation) of a region upstream of the Gs alpha promoter in exon 1A (exon A/B) has been identified in 13 of 13 patients with pseudohypoparathyroidism type IB (renal resistance to parathyroid hormone lacking other AHO associated symptoms) (Liu J et al, 2000; Bastepe M et al, 2001). Pseudohypoparathyroidism type IB shows an imprinted inheritance pattern, ie, the disease is always maternally transmitted (Juppner H et al, 1998). For a summary see Lalande M, 2001. (Mouse 02)Gnas (Gs-alpha), Gnasxl, Nesp, Nespas, F7。Description: Gnas (Gs-alpha), Gnasxl, Nesp, Exon 1A transcript and Nespas (antisense) are transcripts from the Gnas gene locus. Nesp shows maternal expression whereas Gnasxl, and the Exon 1A transcript are paternally expressed (Peters J et al, 1999; Li T et al, 2000; Liu J et al, 2000). Multiple transcripts and protein isoforms are derived from the XL (XXL) promoter (Abramowitz J et al, 2004). Gnas (Gs-alpha) showed biallelic expression in most tissues (Peters J et al, 1999), but preferential expression of the maternal allele in proximal tubule cells and in brown and white adipose tissue (Yu S et al, 1998; Weinstein LS et al, 2000). Gnas imprinting is controlled by the DMR at exon 1A (Williamson CM et al, 2004). Nespas (neuroendocrine secretory protein antisense) is a paternally expressed antisense transcript from the Gnas gene locus (Wroe SF et al, 2000). In addition to the unspliced form there are five alternatively spliced forms of Nespas in mouse (Williamson CM et al, 2002). (Also see Yu S et al, 1998; Williamson CM et al, 1996; Li T et al, 2004). A maternally expressed transcript, F7, between Gnasxl and Exon1a, has been reported (Holmes R et al, 2003). For other studies on the location of methylation imprint marks (possible imprint control regions) see Liu J et al, 2000 and Coombes C et al, 2003 MEG3, MEG3 (GTL2)(14q32 human) 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). Meg3( Gtl2, Gtl2lacZ transgene) (mouse 12)Description: Meg3 (Gtl2) is maternally expressed. There are no obvious open reading frames and it has unknown function (Miyoshi N et al. 2000; Schmidt JV et al. 2000; Takada S et al. 2000). A dwarfism phenotype, resulting from an insertional containing transgene adjacent to Gtl2, was most mutation of a LacZ- strongly expressed when paternally inherited (Schuster-Gossler K et al. 1996). Meg3 lies next to other maternally expressed non-coding RNAs such as a C/D snoRNA cluster of at least nine snoRNAs (see Rian) (Cavaillé J et al. 2002), and a cluster of miRNAs (see Mirg). Croteau S et al, 2003 described multiple splice variants, some of which showed loss of imprinting in mouse crosses. Paternally expressed genes in this region include Rtl(Peg11), Dlk1 and Dio3. This cluster of imprinted genes is conserved with Human 14q32. GTL2 (MEG3)(Sheep 18q IDVGA30-OY3) Description: GTL2 (MEG3) which encodes multiple alternatively spliced nontranslated RNAs is one of 6 imprinted transcripts within a 250 kb region of chromosome 18q. GTL2 is maternally expressed as it is in human and mouse (Charlier C et al 2001). GTL2 and the adjacent gene DLK1 are reciprocally imprinted in human, mouse and sheep and show features similar to IGF2/H19. PEG10, PHLDA2, PWCR1, SNRPN, UBE3A, L3MBTL