Ablondi Michela, Eriksson Susanne, Mikko Sofia
Department of Veterinary Science, Università degli Studi di Parma, Parma, Italy.
Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Uppsala, Sweden.
Anim Genet. 2025 Jun;56(3):e70022. doi: 10.1111/age.70022.
Fragile foal syndrome (FFS) is a disease caused by a recessive lethal missense mutation in the PLOD1 gene located on ECA2. Despite its harmful effect, a relatively high frequency of FFS carriers was observed in Warmblood breeds spanning from 7.4% in a random sample of Swedish Warmblood breed to 17% in the Hanoverian and Danish Warmblood, indicating potential heterozygous advantage. Balancing selection can be further studied based on haplotype blocks and via detection of heterozygosity-rich region (ROHet) around the target of selection. In this study we evaluated the presence of haplotype blocks and ROHet on ECA2 in 380 Swedish Warmblood horses. We compared the results of ROHet with the rest of the genome. On average, 11.7 heterozygosity rich regions were identified per horse on ECA2, with no significant difference in numbers and length compared to what was found in other chromosomes. A unique haplotype block containing 28 markers was found in the FFS haplotype, while there were several haplotype blocks in the non-carrier haplotype. This unique haplotype block mostly spanned the region upstream of the PLOD1 gene and included the MFN2 gene. The presence of this extended haplotype, shared by multiple individuals and including both the FFS variant and the MFN2 gene, suggests that this region may be under selection. While we did not find a clear heterozygosity-rich region around the FFS variant, the extended haplotype may reflect either a signature of balancing selection or linkage disequilibrium with a positively selected variant in MFN2, PLOD1, or nearby loci.
脆弱马驹综合征（FFS）是一种由位于ECA2上的PLOD1基因中的隐性致死错义突变引起的疾病。尽管其具有有害影响，但在温血马品种中观察到FFS携带者的频率相对较高，从瑞典温血马随机样本中的7.4%到汉诺威和丹麦温血马中的17%，这表明可能存在杂合优势。可以基于单倍型块并通过检测选择目标周围的富含杂合性区域（ROHet）来进一步研究平衡选择。在本研究中，我们评估了380匹瑞典温血马ECA2上的单倍型块和ROHet的存在情况。我们将ROHet的结果与基因组的其他部分进行了比较。平均而言，每匹马在ECA2上鉴定出11.7个富含杂合性的区域，与在其他染色体上发现的数量和长度相比，没有显著差异。在FFS单倍型中发现了一个包含28个标记的独特单倍型块，而在非携带者单倍型中有几个单倍型块。这个独特的单倍型块大多跨越PLOD1基因的上游区域，并包括MFN2基因。多个个体共享的这个扩展单倍型的存在，包括FFS变体和MFN2基因，表明该区域可能处于选择之下。虽然我们在FFS变体周围没有发现明确的富含杂合性区域，但这个扩展单倍型可能反映了平衡选择的特征，或者与MFN2、PLOD1或附近位点中一个正选择变体的连锁不平衡。
