Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California-Davis, Davis, California, USA.
Equine Vet J. 2023 Jul;55(4):666-671. doi: 10.1111/evj.13883. Epub 2022 Oct 18.
Equine familial isolated hypoparathyroidism (EFIH) and fragile foal syndrome (FFS) are both fatal recessive conditions reported in Thoroughbred foals. The causal variants for EFIH (RAPGEF5 c.2624C>A; EquCab3.0. chr4: g.54108297G>T) and FFS (PLOD1 c.2032G>A; EquCab3.0, chr2: g.39927817) were recently reported. Prevalence assessment for these variants in a large cohort of samples is needed to provide evidence-based recommendations for genetic testing.
To estimate the frequency of the EFIH and FFS variant alleles in the United States Thoroughbred population between 1988 and 2019, and determine whether these are recent mutations or are increasing in frequency due to current breeding practices.
Population allele frequency study.
Genomic DNA from hair and serum samples were genotyped for the EFIH and FFS. Allele frequencies between cohorts, based on year of birth (1988-2000, n = 728) and (2001-2019, n = 1059), as well as across the seven geographical regions of the United States were compared by Fisher's Exact tests.
EFIH and FFS allele frequencies were not significantly different between the two time points studied (0.008 and 0.004, respectively, in the older cohorts and 0.008 and 0.009 in most recent years). No EFIH or FFS homozygotes were detected. A sample from 1992 was identified as a carrier for EFIH and one from 1993 a carrier for FFS. Non-significant changes in geographical distribution of carriers for both traits were observed.
The earliest samples available for study were from foals born in 1988.
The EFIH and FFS variants are present at low frequency in the United States Thoroughbred population but are not recent mutations. There is no evidence to support changes in allele frequency over time. However, given the closed studbook and breeding practices, continued monitoring of breed allele frequencies and genetic testing is recommended to avoid the mating of carriers and production of affected foals.
马家族性孤立性甲状旁腺功能减退症（EFIH）和脆弱驹综合征（FFS）都是在纯血马驹中报道的致命隐性疾病。EFIH 的致病变体（RAPGEF5 c.2624C>A；EquCab3.0. chr4：g.54108297G>T）和 FFS（PLOD1 c.2032G>A；EquCab3.0，chr2：g.39927817）最近已被报道。需要对大量样本进行这些变体的患病率评估，以便为遗传检测提供循证建议。
估计 1988 年至 2019 年美国纯血马种群中 EFIH 和 FFS 变体等位基因的频率，并确定这些是新出现的突变，还是由于当前的繁殖实践而导致频率增加。
群体等位基因频率研究。
使用毛发和血清样本的基因组 DNA 对 EFIH 和 FFS 进行基因分型。根据出生年份（1988-2000 年，n=728；2001-2019 年，n=1059）对两个队列之间的等位基因频率进行 Fisher 精确检验比较，以及美国七个地理区域之间的等位基因频率比较。
在研究的两个时间点（年龄较大的队列中分别为 0.008 和 0.004，最近几年分别为 0.008 和 0.009），EFIH 和 FFS 等位基因频率没有显著差异。未检测到 EFIH 或 FFS 纯合子。1992 年的一个样本被鉴定为 EFIH 携带者，1993 年的一个样本被鉴定为 FFS 携带者。两种性状携带者的地理分布没有明显变化。
最早可用于研究的样本来自 1988 年出生的驹。
EFIH 和 FFS 变体在美国纯血马种群中的频率较低，但不是新出现的突变。没有证据表明随着时间的推移等位基因频率发生变化。然而，鉴于封闭的血统书和繁殖实践，建议继续监测品种等位基因频率和遗传检测，以避免携带者交配和受影响驹的生产。
