In Silico Prioritization of KISS1 Gene Variants in Cypriot Goats: A Computational Framework for Reproductive, Milk Production, and Kid Growth Trait Validation

This is study provides a framework for in silico and literature-based ranking of KISS1 variants in Cypriot goats (Capra hircus), mainly in terms of their association with reproduction traits, but partly with possible relevance to milk production and kid growth traits. All public caprine KISS1 sequences and all the previously described polymorphisms in goat KISS1 genes have been analyzed in order to select which variants need to be studied further in a particular population. Cypriot goats were considered as the target population, while other studies on Damascus/Shami-type and other breeds of goats served only as background. Polymorphic positions were categorized in terms of genomic location, evidence source, relevance to trait(s), interpretability of coordinate, and confirmation status. Important reference-sequence and coordinate-related inconsistencies have been revealed in this process, underscoring the necessity of reporting both the accession number and coordinate system for each individual variant. Candidate variants were prioritized using an evidence score taking into account Cypriot relevance, reproductive trait relevance, biological plausibility, interpretability of coordinate, and feasibility of genotyping. Sets of primers, predicted PCR-RFLP schemes and functional prediction thresholds were regarded as preliminary tools for future validation. Analysis of GenBank accessions GU142847.1, JX047312.1, and KC989928.1 has shown that coordinates should not be automatically transferred from one reference to another without proper sequence alignment. The first candidate variant is g.893G > C since it has been previously described in Cyprus goats and is associated with litter size. However, the relationship between its coordinate and others needs confirmation. Two more reproductive trait variants are g.2510G > A and g.2540C > T. Since there has been no genotyping, sequencing, and genotype-phenotype correlation study, all the variants and assays proposed need future validation.