Identification of coding polymorphisms in human circadian rhythm genes PER1, PER2, PER3, CLOCK, ARNTL, CRY1, CRY2 and TIMELESS in a multi-ethnic screening panel.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hawkins
Gregory A
GA
Center for Human Genomics, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA. ghawkins@wfubmc.edu
Meyers
Deborah A
DA
Bleecker
Eugene R
ER
Pack
Allan I
AI
D056930:ARNTL Transcription Factors; D001741:Black or African American / Q000235:genetics; D044466:Asian People / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes; D005420:Flavoproteins / Q000235:genetics*; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D007198:Indians, North American / Q000235:genetics; D007199:Indians, South American / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D007585:Jews / Q000235:genetics; D008800:Mexico; D009687:Nuclear Proteins / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D056950:Period Circadian Proteins; D011110:Polymorphism, Genetic; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D044465:White People / Q000235:genetics
D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D056926:CLOCK Proteins; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D005420:Flavoproteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D056950:Period Circadian Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C538960:BMAL1 protein, human; C538963:CRY1 protein, human; C538966:CRY2 protein, human; C539022:PER1 protein, human; C421902:PER2 protein, human; C512644:PER3 protein, human; C509769:TIMELESS protein, human; C538943:CLOCK protein, human