马的13号染色体上的一个区域与马的复发性气道阻塞有关。

A region on equine chromosome 13 is linked to recurrent airway obstruction in horses.

作者信息

Jost U, Klukowska-Rötzler J, Dolf G, Swinburne J E, Ramseyer A, Bugno M, Burger D, Blott S, Gerber V

机构信息

Equine Clinic, Department of Veterinary Clinical Studies, University of Berne, Vetsuisse-Faculty Berne, Linggassstrasse 124, CH-3012 Berne, Switzerland.

出版信息

Equine Vet J. 2007 May;39(3):236-41. doi: 10.2746/042516407x171110.

DOI:10.2746/042516407x171110

PMID:17520975

Abstract

UNLABELLED

REASONS FOR STUDY: Equine recurrent airway obstruction (RAO) is probably dependent on a complex interaction of genetic and environmental factors and shares many characteristic features with human asthma. Interleukin 4 receptor a chain (IL4RA) is a candidate gene because of its role in the development of human asthma, confirmation of this association is therefore required.

METHODS

The equine BAC clone containing the IL4RA gene was localised to ECA13q13 by the FISH method. Microsatellite markers in this region were investigated for possible association and linkage with RAO in 2 large Warmblood halfsib families. Based on a history of clinical signs (coughing, nasal discharge, abnormal breathing and poor performance), horses were classified in a horse owner assessed respiratory signs index (HOARSI 1-4: from healthy, mild, moderate to severe signs). Four microsatellite markers (AHT133, LEX041, VHL47, ASB037) were analysed in the offspring of Sire 1 (48 unaffected HOARSI 1 vs. 59 affected HOARSI 2-4) and Sire 2 (35 HOARSI 1 vs. 50 HOARSI 2-4), age 07 years.

RESULTS

For both sires haplotypes could be established in the order AHT133-LEXO47-VHL47-ASB37. The distances in this order were estimated to be 2.9, 0.9 and 2.3 centiMorgans, respectively. Haplotype association with mild to severe clinical signs of chronic lower airway disease (HOARSI 2-4) was significant in the offspring of Sire 1 (P = 0.026) but not significant for the offspring of Sire 2 (P = 0.32). Linkage analysis showed the ECA13q13 region containing IL4RA to be linked to equine chronic lower airway disease in one family (P<0.01), but not in the second family.

CONCLUSIONS

This supports a genetic background for equine RAO and indicates that IL4RA is a candidate gene with possible locus heterogeneity for this disease.

POTENTIAL RELEVANCE

Identification of major genes for RAO may provide a basis for breeding and individual prevention for this important disease.

摘要

未标记

研究原因：马复发性气道阻塞（RAO）可能取决于遗传和环境因素的复杂相互作用，并且与人类哮喘有许多共同特征。白细胞介素4受体α链（IL4RA）因其在人类哮喘发病中的作用而成为候选基因，因此需要证实这种关联。

方法

通过荧光原位杂交（FISH）方法将包含IL4RA基因的马BAC克隆定位到ECA13q13。在2个大型温血半同胞家族中研究了该区域的微卫星标记与RAO的可能关联和连锁。根据临床症状（咳嗽、鼻分泌物、异常呼吸和性能不佳）的病史，马匹被分类为马主评估的呼吸症状指数（HOARSI 1-4：从健康、轻度、中度到重度症状）。在种公马1（48匹HOARSI 1未受影响 vs. 59匹HOARSI 2-4受影响）和种公马2（35匹HOARSI 1 vs. 50匹HOARSI 2-4）的后代中分析了4个微卫星标记（AHT133、LEX041、VHL47、ASB037），年龄为07岁。

结果

对于两个种公马，单倍型可以按AHT133-LEXO47-VHL47-ASB37的顺序确定。按此顺序的距离估计分别为2.9、0.9和2.3厘摩。在种公马1的后代中，单倍型与慢性下气道疾病的轻度至重度临床症状（HOARSI 2-4）的关联显著（P = 0.026），但在种公马2的后代中不显著（P = 0.32）。连锁分析表明，包含IL4RA的ECA13q13区域在一个家族中与马慢性下气道疾病连锁（P<0.01），但在第二个家族中不连锁。