Whole genome sequencing of pairwise human subjects reveals DNA mutations specific to developmental dysplasia of the hip
| Autor: | Jianfeng Fang, Zhi-Xiong Guo, Jin Dai, Xing-guang Chen, Yun-fang Zhen, Chunhua Yin, Lun-qing Zhu, Xiao-dong Wang, Wen-Yan Zhang, Zhen-hua Zhu, Guang-Hao Su, Cheng-da Zou, Ya Zhang, Fu-Yong Zhang, Cai-ying Xu |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Adult
Male 0106 biological sciences Biology 01 natural sciences Genetic analysis DNA sequencing 03 medical and health sciences chemistry.chemical_compound Osteogenesis Genetics medicine Genetic predisposition Humans Hip Dislocation Congenital Gene 030304 developmental biology Hip dysplasia Whole genome sequencing 0303 health sciences Whole Genome Sequencing Infant medicine.disease Pedigree chemistry Dysplasia Child Preschool Mutation Female DNA 010606 plant biology & botany |
| Zdroj: | Genomics. 111:320-326 |
| ISSN: | 0888-7543 |
| Popis: | Developmental dysplasia of the hip (DDH) is a common congenital malformation characterized by mismatch in shape between the femoral head and acetabulum, and leads to hip dysplasia. To date, the pathogenesis of DDH is poorly understood and may involve multiple factors, including genetic predisposition. However, comprehensive genetic analysis has not been applied to investigate a genetic component of DDH. In the present study, 10 pairs of healthy fathers and DDH daughters were enrolled to identify genetic hallmarks of DDH using high throughput whole genome sequencing. The DDH-specific DNA mutations were found in each patient. Overall 1344 genes contained DDH-specific mutations. Functional enrichment analysis showed that these genes played important roles in the cytoskeleton, microtubule cytoskeleton, sarcoplasm and microtubule associated complex. These functions affected osteoblast and osteoclast development. Therefore, we proposed that the DDH-specific mutations might affect bone development, and caused DDH. Our pairwise high throughput sequencing results comprehensively delineated genetic hallmarks of DDH. Further research into the biological impact of these mutations may inform the development of DDH diagnostic tools and allow neonatal gene screening. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect