近日,，《自然—遺傳學(xué)》（Nature Genetics）上發(fā)表的一項(xiàng)研究成功稱(chēng),，共有的遺傳基礎(chǔ)可導(dǎo)致人類(lèi)患上一種存在于黃金獵犬身上的罕見(jiàn)皮膚病,。
這種皮膚病我們稱(chēng)之為先天性魚(yú)鱗病,，患有此病的人在出生后不久,，全身皮膚會(huì)呈現(xiàn)魚(yú)鱗狀。Catherine André, Judith Fischer與其他研究人員通過(guò)研究犬類(lèi)獨(dú)特的繁殖歷史,，從患有該病的黃金獵犬身上鑒別出了致病基因,，并將其命名為PNPLA1。通過(guò)進(jìn)一步分析PNPLA1,，研究人員發(fā)現(xiàn),，患有類(lèi)似皮膚病的人身上同樣存在該基因，并且在每?jī)蓚€(gè)家族中,，就有六個(gè)人攜帶有這種基因的兩種分裂類(lèi)型,。
PNPLA1基因通過(guò)皮膚表皮層表達(dá)，對(duì)維持皮膚的屏障功能具有重要影響,。其所屬的蛋白家族可改變類(lèi)脂結(jié)構(gòu),，包括形成細(xì)胞外膜的類(lèi)脂種類(lèi)。（生物谷 Bioon.com）
doi:10.1038/ng.1056
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PNPLA1 mutations cause autosomal recessive congenital ichthyosis in golden retriever dogs and humans
Anaïs Grall, Eric Guaguère, Sandrine Planchais, Susanne Grond, Emmanuelle Bourrat, Ingrid Hausser, Christophe Hitte, Matthieu Le Gallo, Céline Derbois, Gwang-Jin Kim, Laëtitia Lagoutte, Frédérique Degorce-Rubiales, Franz P W Radner, Anne Thomas, Sébastien Küry, Emmanuel Bensignor, Jacques Fontaine, Didier Pin, Robert Zimmermann, Rudolf Zechner, Mark Lathrop, Francis Galibert, Catherine André & Judith Fischer
Ichthyoses comprise a heterogeneous group of genodermatoses characterized by abnormal desquamation over the whole body, for which the genetic causes of several human forms remain unknown. We used a spontaneous dog model in the golden retriever breed, which is affected by a lamellar ichthyosis resembling human autosomal recessive congenital ichthyoses (ARCI), to carry out a genome-wide association study. We identified a homozygous insertion-deletion (indel) mutation in PNPLA1 that leads to a premature stop codon in all affected golden retriever dogs. We subsequently found one missense and one nonsense mutation in the catalytic domain of human PNPLA1 in six individuals with ARCI from two families. Further experiments highlighted the importance of PNPLA1 in the formation of the epidermal lipid barrier. This study identifies a new gene involved in human ichthyoses and provides insights into the localization and function of this yet uncharacterized member of the PNPLA protein family.
