Center for Companion Animal Health, School of Veterinary Medicine, University of California, One Shields Avenue, Davis, CA 95616, USA.
Virus Res. 2013 Jul;175(1):58-63. doi: 10.1016/j.virusres.2013.04.006. Epub 2013 Apr 22.
Genetic factors are presumed to influence the incidence of feline infectious peritonitis (FIP), especially among pedigreed cats. However, proof for the existence of such factors has been limited and mainly anecdotal. Therefore, we sought evidence for genetic susceptibility to FIP using feline high density single nucleotide polymorphism (SNP) arrays in a genome-wide association study (GWAS). Birman cats were chosen for GWAS because they are highly inbred and suffer a high incidence of FIP. DNA from 38 Birman cats that died of FIP and 161 healthy cats from breeders in Denmark and USA were selected for genotyping using 63K SNPs distributed across the feline genome. Danish and American Birman cats were closely related and the populations were therefore combined and analyzed in two manners: (1) all cases (FIP) vs. all controls (healthy) regardless of age, and (2) cases 1½ years of age and younger (most susceptible) vs. controls 2 years of age and older (most resistant). GWAS of the second cohort was most productive in identifying significant genome-wide associations between case and control cats. Four peaks of association with FIP susceptibility were identified, with two being identified on both analyses. Five candidate genes ELMO1, RRAGA, TNFSF10, ERAP1 and ERAP2, all relevant to what is known about FIP virus pathogenesis, were identified but no single association was fully concordant with the disease phenotype. Difficulties in doing GWAS in cats and interrogating complex genetic traits were discussed.
遗传因素被认为会影响猫传染性腹膜炎（FIP）的发病率，特别是在纯种猫中。然而，证明这些因素存在的证据有限且主要是轶事证据。因此，我们使用猫的高密度单核苷酸多态性（SNP）阵列在全基因组关联研究（GWAS）中寻找对 FIP 的遗传易感性的证据。选择伯曼猫进行 GWAS，是因为它们高度近亲繁殖并且 FIP 发病率很高。从死于 FIP 的 38 只伯曼猫和丹麦和美国的繁殖者的 161 只健康猫中选择 DNA 进行基因分型，使用分布在猫基因组中的 63K SNP 进行基因分型。丹麦和美国的伯曼猫密切相关，因此将种群合并并以两种方式进行分析：（1）无论年龄大小，所有病例（FIP）与所有对照（健康）相比，以及（2）年龄在 1 岁半以下（最易感）与年龄在 2 岁及以上的对照（最抵抗）相比。对第二个队列的 GWAS 最能确定病例和对照猫之间与 FIP 易感性相关的全基因组显著关联。确定了与 FIP 易感性相关的四个关联峰，其中两个在两种分析中都被确定。确定了五个候选基因 ELMO1、RRAGA、TNFSF10、ERAP1 和 ERAP2，它们都与已知的 FIP 病毒发病机制有关，但没有一个单一的关联与疾病表型完全一致。讨论了在猫中进行 GWAS 和检测复杂遗传特征的困难。
