Genomic cloning and characterization of the human homeobox gene SIX6 reveals a cluster of SIX genes in chromosome 14 and associates SIX6 hemizygosity with bilateral anophthalmia and pituitary anomalies
Genomic cloning and characterization of the human homeobox gene SIX6 reveals a cluster of SIX genes in chromosome 14 and associates SIX6 hemizygosity with bilateral anophthalmia and pituitary anomalies
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DOI：
10.1006/geno.1999.5916
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发表时间：
1999-10-01
期刊：
影响因子：
4.4
通讯作者：
de Córdoba, SR
中科院分区：
文献类型：
--
作者：
Gallardo, ME;Lopez-Rios, J;de Córdoba, SR
果蝇基因sine oculis（so）是眼睛发育所需的核同源蛋白，在脊椎动物中有几个同源物（SLY基因家族）。其中，SIX 3被认为是so的功能性直向同源物，因为它在发育中的眼睛中强烈表达。然而，胚胎SIX 3的表达并不局限于眼睛，并且已经发现SIX 3在一些无前脑畸形2型（HPE 2）患者中发生突变，这表明SIX 3在头部发育中具有广泛的意义。我们在这里报告的SIX 6，一个新的人类SLP基因，是鸡Six 6（Optx 2）基因的同源物的克隆和表征。SIX 6与SIX 3密切相关，并在发育和成年人视网膜中表达。数据来自。鸡和小鼠的研究表明，人SIX 6基因也在下丘脑和垂体区域表达。SIX 6跨越2567 bp的基因组DNA，并被分成两个外显子，转录成1393个核苷酸长的mRNA。SIX 6的染色体定位结果表明，SIX 6与SIX 1和SIX 4在人类染色体14q22.3-q23上紧密连锁，为脊椎动物SIX家族的起源和进化提供了线索。最近有三个独立的报告与双侧无眼症和垂体异常相关的14q22.3-q23间质缺失。其中一例的基因组分析显示SIX 6半合子，强烈表明SIX 6单倍不足是这些发育障碍的原因。(C)北京：科学出版社.
The Drosophila gene sine oculis (so), a nuclear homeoprotein that is required for eye development, has several homologues in vertebrates (the SLY gene family). Among them, SIX3 is considered to be the functional orthologue of so because it is strongly expressed in the developing eye. However, embryonic SIX3 expression is not Limited to the eye held, and SIX3 has been found to be mutated in some patients with holoprosencephaly type 2 (HPE2), suggesting that SIX3 has wide implications in head development. We report here the cloning and characterization of SIX6, a novel human SLP gene that is the homologue of the chick Six6(Optx2) gene. SIX6 is closely related to SIX3 and is expressed in the developing and adult human retina. Data from. chick and mouse suggest that the human SIX6 gene is also expressed in the hypothalamic and the pituitary regions. SIX6 spans 2567 bp of genomic DNA and is split in two exons that are transcribed into a 1393-nucleotide-long mRNA. Chromosomal mapping of SIX6 revealed that it is closely linked to SIX1 and SIX4 in human chromosome 14q22.3-q23, which provides clues about the origin and evolution of the vertebrate SIX family. Recently three independent reports have associated interstitial deletions at 14q22.3-q23 with bilateral anophthalmia and pituitary anomalies. Genomic analyses of one of these cases demonstrated SIX6 hemizygosity, strongly suggesting that SIX6 haploinsufficiency is responsible for these developmental disorders. (C) 1999 Academic Press.