Hawkins Gregory A, Meyers Deborah A, Bleecker Eugene R, Pack Allan I
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
DNA Seq. 2008 Feb;19(1):44-9. doi: 10.1080/10425170701322197.
In this study, the exonic regions of the circadian rhythm genes PER1, PER2, PER3, CLOCK, ARNTL, CRY1, CRY2 and TIMELESS were re-sequenced and coding changes identified in a panel of 95 individuals varying in ethnicity.
DNA screening panel consisting of 95 DNA samples (17 American Caucasians, 17 African Americans, 8 Ashkenazi Jews, 8 Chinese, 8 Japanese, 5 Mexican Indians, 8 Mexicans, 8 Northern Europeans, 8 Puerto Ricans, and 8 South Americans) selected from the Coriell Institute Human Variation Panel.
In addition to coding changes already identified in the database dbSNP, novel coding changes were identified, including PER1: Pro37Ser, Pro351Ser, Gln988Pro, Ala998Thr; PER2: Leu83Arg, Leu157Leu, Thre174Ile, Phe400Phe, Pro822Pro, Ala828Thr, Ala861Val, Phe876Leu, Val883Met, Val903Ile, Ala923Pro; PER3: Pro67Pro, Val90Ile, His638His, Ala820Ala, Leu929Leu; ARNTL: Arg166Gln, Ser459Phe; CLOCK: Ala34Ala, Ser208Cys, Phe233Phe, Ser632Thr, Ser816Ser; TIMELESS: Met870Val and CRY2: His35His. No coding polymorphisms were identified in CRY1.
Considerable genetic variation occurs within the coding region of the genes regulating circadian rhythm. Many of the non-synonymous coding polymorphisms could affect protein structure/function with the potential to affect molecular regulation of the sleep/wake cycle. Many of the potential functional effects could be ethnic group specific.
在本研究中，对昼夜节律基因PER1、PER2、PER3、CLOCK、ARNTL、CRY1、CRY2和TIMELESS的外显子区域进行重新测序，并在95名不同种族的个体中鉴定编码变化。
从科里尔研究所人类变异样本库中选取了由95个DNA样本组成的DNA筛查样本组（17名美国白种人、17名非裔美国人、8名德系犹太人、8名中国人、8名日本人、5名墨西哥印第安人、8名墨西哥人、8名北欧人、8名波多黎各人以及8名南美洲人）。
除了在数据库dbSNP中已鉴定出的编码变化外，还鉴定出了新的编码变化，包括PER1：Pro37Ser、Pro351Ser、Gln988Pro、Ala998Thr；PER2：Leu83Arg、Leu157Leu、Thre174Ile、Phe400Phe、Pro822Pro、Ala828Thr、Ala861Val、Phe876Leu、Val883Met、Val903Ile、Ala923Pro；PER3：Pro67Pro、Val90Ile、His638His、Ala820Ala、Leu929Leu；ARNTL：Arg166Gln、Ser459Phe；CLOCK：Ala34Ala、Ser208Cys、Phe233Phe、Ser632Thr、Ser816Ser；TIMELESS：Met870Val以及CRY2：His35His。在CRY1中未鉴定出编码多态性。
调节昼夜节律的基因编码区域存在相当大的遗传变异。许多非同义编码多态性可能会影响蛋白质结构/功能，从而有可能影响睡眠/觉醒周期的分子调节。许多潜在的功能效应可能具有种族特异性。
