Additional file 1: Supplementary Tables. of Whole-body patterns of the range of joint motion in young adults: masculine type and feminine type

Table S1. Age, hand/arm and foot/leg dominances, and experience of sports of the subjects dominances of the subjects. Table S2. Somatometric and sthenometric measurements in the subjects. (DOCX 23 kb

An ancestral haplotype of the human <i>PERIOD2</i> gene associates with reduced sensitivity to light-induced melatonin suppression

<div><p>Humans show various responses to the environmental stimulus in individual levels as “physiological variations.” However, it has been unclear if these are caused by genetic variations. In this study, we examined the association between the physiological variation of response to light-stimulus and genetic polymorphisms. We collected physiological data from 43 subjects, including light-induced melatonin suppression, and performed haplotype analyses on the clock genes, <i>PER2</i> and <i>PER3</i>, exhibiting geographical differentiation of allele frequencies. Among the haplotypes of <i>PER3</i>, no significant difference in light sensitivity was found. However, three common haplotypes of <i>PER2</i> accounted for more than 96% of the chromosomes in subjects, and 1 of those 3 had a significantly low-sensitive response to light-stimulus (<i>P</i> < 0.05). The homozygote of the low-sensitive <i>PER2</i> haplotype showed significantly lower percentages of melatonin suppression (<i>P</i> < 0.05), and the heterozygotes of the haplotypes varied their ratios, indicating that the physiological variation for light-sensitivity is evidently related to the <i>PER2</i> polymorphism. Compared with global haplotype frequencies, the haplotype with a low-sensitive response was more frequent in Africans than in non-Africans, and came to the root in the phylogenetic tree, suggesting that the low light-sensitive haplotype is the ancestral type, whereas the other haplotypes with high sensitivity to light are the derived types. Hence, we speculate that the high light-sensitive haplotypes have spread throughout the world after the Out-of-Africa migration of modern humans.</p></div

Comparison of the distributions of melatonin suppression for the genotypes of <i>PER2</i>.

<p>The thick middle lines in the boxes represent the medians, the tops and bottoms of the boxes represent the third and the first quartiles, respectively, and the lower and upper error bars indicate the minimum and the maximum values. One dot represents one subject, and the numbers of individuals, N, are shown in the parentheses. In the case of heterozygote, differently colored dots represent different genotypes. The Kruskal-Wallis test and Scheffe’s method of multiple comparison tests were conducted, and the pairs of Hap1-Hap3 and Hap2-Hap3 homozygotes showed significant differences.</p

Summary of subjects’ physiological characteristics.

<p>Summary of subjects’ physiological characteristics.</p

SNPs examined in the <i>PER2</i> gene and frequencies of the haplotypes in the global populations.

<p>(A) Relative map for the six SNPs examined. The SNPs examined in this study are numbered serially, and their rs numbers, alleles reported, and allele frequencies of JPT in the HapMap database are shown. For the SNP6, the amino acid change (Gly/Glu) has been reported in dbSNP. (B) Ancestral allele frequencies of SNPs in <i>PER2</i>. The allele frequency data from Japan are divided into four groups: subjects with physiological data, Northern Kyushu, Ryukyu, and JPT. Those are compared to three approximate geographic populations: East Asia (CHB, CHS), Europe (CEU, FIN, GBR, IBS, TSI) and Africa (LWK, YRI) from the 1000 Genomes Project database. (C) Haplotype frequencies of <i>PER2</i> in each geographical region. The numbers of local populations included in the geographical region are shown in parentheses. The N represents the numbers of the individuals. The combined frequencies of the remaining haplotype (Residuals) are less than 1.0% in all the geographical regions, indicating that each haplotype in the residual is extremely uncommon among the samples examined.</p

Contribution of <i>FGFR1</i> Variants to Craniofacial Variations in East Asians

<div><p><i>FGFR1</i> plays an important role in the development of the nervous system as well as the regulation of the skeletal development and bone homeostasis. Mutations in <i>FGFR1</i> genes affect skull development, specifically suture and synchondrosis, resulting in craniosynostosis and facial abnormalities. We examined subjects with normal skull morphology for genetic polymorphisms that might be associated with normal craniofacial variations. Genomic DNA was obtained from 216 Japanese and 227 Korean subjects. Four <i>FGFR1</i> SNPs, namely, rs881301, rs6996321, rs4647905, and rs13317, were genotyped. These SNPs were tested for association with craniofacial measurements obtained from lateral and posteroanterior cephalometries, in which principle component analysis was performed to compress the data of the craniofacial measurements. We observed that SNPs rs13317 and rs6996321 were correlated with the overall head size and midfacial development, indicating that <i>FGFR1</i> SNPs played crucial roles in the normal variation of human craniofacial morphology. Subjects with the derived alleles of SNPs rs13317 and rs6996321 had a small face and a facial pattern associated with a retruded midface and relatively wide-set eyes. These facial features were similar to but were milder than those of individuals with Pfeiffer syndrome, which is caused by a dysfunctional mutation in <i>FGFR1</i>.</p></div

Allele frequencies and LD coefficients of <i>FGFR1</i> SNPs.

<p>Allele frequencies and LD coefficients of <i>FGFR1</i> SNPs.</p

PC loading for each PC. (A) PCA of cranial measurements. (B) PCA of mandibular measurements.

<p>PC loading for each PC. (A) PCA of cranial measurements. (B) PCA of mandibular measurements.</p

Regression analysis to determine the association of FGFR1 SNPs with craniofacial morphological variation in Japanese and Korean subjects.

<p>Regression analysis to determine the association of FGFR1 SNPs with craniofacial morphological variation in Japanese and Korean subjects.</p

Lateral and posteroanterior cephalometric tracing showing the landmarks used to obtain craniofacial measurements.

<p>(V) Vertex, (Eu) eunion, (Lo) latero-orbitale, (Or) orbitale, (Zy) zygion, (Cd) condylion, (Ko) Koronoid, (Ma) mastoid, (NC) nasal cavity, (Cr) crista galli, (ANS) anterior nasal spine, (Go) gonion, (Ag) antegonion, (Me) menton, (G) glabella, (N) nasion, (S) sella turcica, (SOr) supra orbitale, (R) rhinion, (KR) key ridge, (Pr) prosthion, (A) point A, (PNS) posterior nasal spine, (Id) infradentale, (Gn) gnathion. The NA plane was used as a reference to measure the anteroposterior position of G, SOr, R, Or, and KR, with positive and negative values indicating whether the landmark is in an anterior and posterior direction, respectively, from the NA plane.</p