Chromosomal imbalance in pigs showing a syndromic form of cleft palate
Chromosomal imbalance in pigs showing a syndromic form of cleft palate
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DOI：
10.1186/s12864-019-5711-4
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发表时间：
2019-05-08
期刊：
影响因子：
4.4
通讯作者：
Drogemuller, Cord
中科院分区：
文献类型：
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作者：
Grahofer, Alexander;Letko, Anna;Drogemuller, Cord
背景腭裂或腭裂是一种已知的异常猪导致他们的死亡。然而，对其病因知之甚少。详细描述的表型来自尸检和计算机断层扫描显示，所有20例还表现出缺牙和肾囊肿。此外，假定的遗传起源，由于显性遗传的所有20个记录的情况下，确认后代的一个单一的board.ResultsSingle核苷酸变异（SNV）基因分型数据被用来映射在猪基因组中的缺陷，并导致在受影响的后代中的染色体不平衡的检测。一个受影响的仔猪和一个正常的全同胞的全基因组测序被用来确定染色体易位和精细定位基因组中的断点。最后，我们证明了产生畸形仔猪的公猪携带平衡易位。在核型分析过程中，先前未观察到检测到的8号和14号染色体Mb大小片段的易位。所有受影响的后代被证明是携带者的染色体14，包括FGFR2基因，这是与各种显性遗传颅面骨发育不全综合征的人，和部分单体的染色体8含有MSX1已知与牙齿发育不全和orofacial clefts在其他species.ConclusionsThis研究说明了最近建立的基因组资源在猪的有用性。在这项研究中，全基因组基因分型和测序方法的应用允许责任公猪和观察到的缺陷的遗传原因的鉴定。通过实施系统监测，可以在早期阶段发现遗传缺陷，避免先天性疾病的进一步传播。
BackgroundPalatoschisis or cleft palate is a known anomaly in pigs resulting in their death. However, little is known about its aetiology. A detailed description of the phenotype was derived from necropsy and by computed tomography revealing that all 20 cases also exhibited hypodontia and renal cysts. Furthermore, a genetic origin was assumed due to dominant inheritance as all 20 recorded cases were confirmed offspring of a single boar.ResultsSingle nucleotide variant (SNV) genotyping data were used to map the defect in the porcine genome and led to the detection of a chromosomal imbalance in the affected offspring. Whole genome sequencing of an affected piglet and a normal full sib was used to identify a chromosomal translocation and to fine map the breakpoints in the genome. Finally, we proved that the boar, which sired the malformed piglets, carried a balanced translocation. The detected translocation of Mb-sized segments of chromosome 8 and 14 had not been previously observed during karyotyping. All affected offspring were shown to be carriers of a partial trisomy of chromosome 14 including the FGFR2 gene, which is associated with various dominant inherited craniofacial dysostosis syndromes in man, and partial monosomy of chromosome 8 containing MSX1 known to be associated with tooth agenesis and orofacial clefts in other species.ConclusionsThis study illustrates the usefulness of recently established genomic resources in pigs. In this study, the application of genome-wide genotyping and sequencing methods allowed the identification of the responsible boar and the genetic cause of the observed defect. By implementing systematic surveillance, it is possible to identify genetic defects at an early stage and avoid further distribution of congenital disorders.