Runs of homozygosity associated with speech delay in autism in a taiwanese han population: evidence for the recessive model.
Runs of homozygosity (ROH) may play a role in complex diseases. In the current study, we aimed to test if ROHs are linked to the risk of autism and related language impairment. We analyzed 546,080 SNPs in 315 Han Chinese affected with autism and 1,115 controls. ROH was defined as an extended homozyg...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3745408?pdf=render |
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| author | Ping-I Lin Po-Hsiu Kuo Chia-Hsiang Chen Jer-Yuarn Wu Susan S-F Gau Yu-Yu Wu Shih-Kai Liu |
| author_facet | Ping-I Lin Po-Hsiu Kuo Chia-Hsiang Chen Jer-Yuarn Wu Susan S-F Gau Yu-Yu Wu Shih-Kai Liu |
| author_sort | Ping-I Lin |
| collection | DOAJ |
| description | Runs of homozygosity (ROH) may play a role in complex diseases. In the current study, we aimed to test if ROHs are linked to the risk of autism and related language impairment. We analyzed 546,080 SNPs in 315 Han Chinese affected with autism and 1,115 controls. ROH was defined as an extended homozygous haplotype spanning at least 500 kb. Relative extended haplotype homozygosity (REHH) for the trait-associated ROH region was calculated to search for the signature of selection sweeps. Totally, we identified 676 ROH regions. An ROH region on 11q22.3 was significantly associated with speech delay (corrected p = 1.73×10(-8)). This region contains the NPAT and ATM genes associated with ataxia telangiectasia characterized by language impairment; the CUL5 (culin 5) gene in the same region may modulate the neuronal migration process related to language functions. These three genes are highly expressed in the cerebellum. No evidence for recent positive selection was detected on the core haplotypes in this region. The same ROH region was also nominally significantly associated with speech delay in another independent sample (p = 0.037; combinatorial analysis Stouffer's z trend = 0.0005). Taken together, our findings suggest that extended recessive loci on 11q22.3 may play a role in language impairment in autism. More research is warranted to investigate if these genes influence speech pathology by perturbing cerebellar functions. |
| first_indexed | 2024-12-11T22:18:58Z |
| format | Article |
| id | doaj.art-67926c81161740dea50e789bb8da923d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T22:18:58Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-67926c81161740dea50e789bb8da923d2022-12-22T00:48:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-0188e7205610.1371/journal.pone.0072056Runs of homozygosity associated with speech delay in autism in a taiwanese han population: evidence for the recessive model.Ping-I LinPo-Hsiu KuoChia-Hsiang ChenJer-Yuarn WuSusan S-F GauYu-Yu WuShih-Kai LiuRuns of homozygosity (ROH) may play a role in complex diseases. In the current study, we aimed to test if ROHs are linked to the risk of autism and related language impairment. We analyzed 546,080 SNPs in 315 Han Chinese affected with autism and 1,115 controls. ROH was defined as an extended homozygous haplotype spanning at least 500 kb. Relative extended haplotype homozygosity (REHH) for the trait-associated ROH region was calculated to search for the signature of selection sweeps. Totally, we identified 676 ROH regions. An ROH region on 11q22.3 was significantly associated with speech delay (corrected p = 1.73×10(-8)). This region contains the NPAT and ATM genes associated with ataxia telangiectasia characterized by language impairment; the CUL5 (culin 5) gene in the same region may modulate the neuronal migration process related to language functions. These three genes are highly expressed in the cerebellum. No evidence for recent positive selection was detected on the core haplotypes in this region. The same ROH region was also nominally significantly associated with speech delay in another independent sample (p = 0.037; combinatorial analysis Stouffer's z trend = 0.0005). Taken together, our findings suggest that extended recessive loci on 11q22.3 may play a role in language impairment in autism. More research is warranted to investigate if these genes influence speech pathology by perturbing cerebellar functions.http://europepmc.org/articles/PMC3745408?pdf=render |
| spellingShingle | Ping-I Lin Po-Hsiu Kuo Chia-Hsiang Chen Jer-Yuarn Wu Susan S-F Gau Yu-Yu Wu Shih-Kai Liu Runs of homozygosity associated with speech delay in autism in a taiwanese han population: evidence for the recessive model. PLoS ONE |
| title | Runs of homozygosity associated with speech delay in autism in a taiwanese han population: evidence for the recessive model. |
| title_full | Runs of homozygosity associated with speech delay in autism in a taiwanese han population: evidence for the recessive model. |
| title_fullStr | Runs of homozygosity associated with speech delay in autism in a taiwanese han population: evidence for the recessive model. |
| title_full_unstemmed | Runs of homozygosity associated with speech delay in autism in a taiwanese han population: evidence for the recessive model. |
| title_short | Runs of homozygosity associated with speech delay in autism in a taiwanese han population: evidence for the recessive model. |
| title_sort | runs of homozygosity associated with speech delay in autism in a taiwanese han population evidence for the recessive model |
| url | http://europepmc.org/articles/PMC3745408?pdf=render |
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