Cutaneous malignant melanoma in Sinclair swine is a hereditary disease that develops in utero or during the first 6 weeks of life. In many cases, the tumors regress and piglets survive the disease. Two different sets of gene(s) might be involved in the disease: tumor initiator (suppressor) locus or loci and loci affecting the aggressiveness of the disease (number and stage of tumors). We develop maximum-likelihood methods for interval mapping for both types of loci. The experimental design consisted of a boar mated to tumor-bearing sows with recording of tumor status and number of tumors in the 6 weeks of life of the offspring. The model to search for the tumor initiator locus (with alleles T and t) was tested by computer simulation. Estimates of penetrances (Psi(TT) and Psi(Tt) for genotypes TT and Tt, respectively) were accurate even for small family sizes. Statistical power was >99% for a family size of 70 with Psi(TT) = 1 and Psi(Tt) = 0. The models to test for number of tumors incorporated genotype information for the tumor initiator locus. All models were tested with data from a single boar family of 72 piglets over swine chromosomes 6 and 8 (SSC6 and SSC8). No tumor evidence for initiator loci was found associated with these chromosomes. However, association of a QTL affecting number of tumors at birth near microsatellite SW1953 on SSC8 was chromosomewise significant (P<0.0124).

译文

:辛克莱猪的慢性恶性黑色素瘤是一种遗传性疾病,会在子宫内或生命的前6周内发展。在许多情况下,肿瘤消退,仔猪在疾病中幸存下来。该疾病可能涉及两套不同的基因:肿瘤引发剂(抑制子)基因座或基因座,以及影响疾病侵袭性(肿瘤的数量和阶段)的基因座。我们为两种基因座的区间作图开发了最大似然法。实验设计包括一个与带有肿瘤的母猪交配的公猪,并记录后代6周内的肿瘤状态和肿瘤数量。通过计算机模拟测试了用于寻找肿瘤引发剂基因座(具有等位基因T和t)的模型。外显率的估计(基因型TT和Tt分别为Psi(TT)和Psi(Tt))即使对于小型家庭来说也很准确。对于Psi(TT)= 1和Psi(Tt)= 0的70个家庭,统计功效> 99%。用于测试肿瘤数量的模型并入了肿瘤起始基因位点的基因型信息。所有模型均使用来自猪的第6和8号染色体(SSC6和SSC8)的72个仔猪的单个公猪家族的数据进行了测试。没有发现与这些染色体相关的起始位点的肿瘤证据。但是,影响SSC8上微卫星SW1953附近出生时肿瘤数量的QTL的关联在染色体上是显着的(P <0.0124)。

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