Five gene loci appear to define the morphologic shape of a human face. According to Liu et al. in PLOS Genetics 2012|8|9|e1002932, they are located in and around the PRDM16 gene on chromosome 1, the chromosome 2 gene PAX3, TP63 on chromosome 3, C5orf50 on chromosome 5, and the COL17A1 gene on chromosome 10. These findings came from a genome-wide association study (GWAS) performed by members of the International Visible Trait Genetics, or VisiGen, Consortium where several Affymetrix and/or Illumina arrays were used to identify these loci.
Facial features, in this case were studied in close to 10,000 volunteering Europeans, range from nose width and height to the distance between a person's eyes. The Consortium studied volunteers of European ancestry living in the Netherlands, Australia, Germany, Canada, and the United Kingdom. The group used 3D MRI based phenotyping together with autosomal single-nucleotide-polymorphism (SNP) analysis to extract facial landmarks and to find association for the 48 identified facial phenotypes. They were able to identify common DNA variants within the five genetic loci which led the researchers to conclude that these genes are associated with normal facial shape phenotypes in individuals of European ancestry.
We can notice differences in facial shape in other individuals when we go out for dinner, look around in a bar, attend social meetings or walk around in a park or the streets of a city. Variations of facial shapes are one of the most noticeable phenotype in humans. Clearly the facial morphology in humans is under genetic regulation. For example, monozygotic twins look more alike than dizygotic twins or other siblings or even unrelated individuals. This indicates that human facial morphology has a strong genetic component. This study identified the genes that are essential for the development of the craniofacial morphology in humans and provided novel links between common DNA variants and normal variation in human facial morphology and confirmed known ones as well. However, more genes that participate in the regulation of these five genes may need to be identified to allow for the prediction of a facial shape from DNA data to be useful for future forensic applications. Already scientists are able to predict certain eye and hair colors with high accuracies using DNA analysis. Table 1 shows the identified genes, their chromosome location as well as the SNPs of the identified genes.
Table 1: The five identified genes are listed as well as the sequences of the SNPs involved.
Gene
|
Chromosome
|
SNP
|
Sequence
|
PRDM16
|
1p36.23-p33
|
TCTGTGGGGCCCTTTGCAACCTCCCT[C/T]ATGCATGAGCAATTCAGGGGTTTGA
| |
PAX3
|
2q35
|
ACAAATTTTAAAAATTAATTTAAAAA[C/T]TCTGTTCTGTTTAACACTAATAATC
| |
TP63
|
3q28
|
rs17447439
|
CCAGGTGCTCATTTGATGATAGCAGC[A/G]TGAAGCTCTTCCCATTCTGCACCGT
|
C5orf50
|
5q35.1
|
TCCAATCCTCTCATCTGTCCCTCTAA[C/T]GGGCTCCGACAGATCACTCCACAGT
| |
COL17A1
|
10q24.3
|
CATACCTTTGGGTCCTGGTGGTCCCA[C/T]TGGTCCTTTGTCACCTAAAAAGGAA
|
Source: Liu et al., PLOS September 2012; NCBI SNP Database: http://www.ncbi.nlm.nih.gov/snp?term=rs805722
Figure 1: Nature and location of a single-nucleotide polymorphism (SNP). (Left) The chromosomal location of the gene PRDM16 in chromosome 1p36.23-p33 and the info for SNP rs4648379 for humans (Homo sapiens) is illustrated. (Right) The nature of a SNP (pronounced snip) within a DNA sequence is illustrated as well. A SNP is a variation that occurs when a single nucleotide - A, T, C or G - in the genome differs between members of a biological species or paired chromosomes in an individual (Source: NCBI and Wikipedia).
The following shows the location of a SNP within a gene. The sequence highlighted in grey depicts the sequence of the SNP probe.
>gnl|dbSNP|rs4648379|allelePos=501|totalLen=1001|taxid=9606|snpclass=1|alleles='C/T'|mol=Genomic|build=137
TTGCCTTTAA GTCTTTGGAC ATATTTATAA GGTATTTTTA AATCTGCTGA TTCTAACATC
TGGCTCATAT CAGAGTTGGT TTGGATTGGC TGTGGTTTTT TCTAGGCTAT GGGTGACAAT
TTCCTGTTTC TGTGCACATT TAGTAATTTT TTATTGTATT GGATGTTGTA GATGACATTG
TAGAAACTCT GGATTCTGTT GTATTCCTCT GAAAAGTTTT GGTTTTGGTT CTAGAGAGAG
TTTCAATCAC TAGGTGCTCA CCCTGAGTTT GCAGAAGTGT GGCTCTACAC TTTATTAGGT
TGGGTCTTCT TCTGTTTTAT CTTTAGGATT AGTCTTTGTT CTTAAGGCTC AGCCCTTCTG
GGACTTTAGT GGAAAGCCAA AGGTGATCAT CAAGCTCTTC TAAGTTGATG GGACTCAAAT
TCCAAAGCCC TGCTGTGGTA AGCAGCAAGT GAAATCTCTG TGTAGCTCTT GTTTTCTGTG
GGGCCCTTTG CAACCTCCCT
Y
ATGCATGAGC AATTCAGGGG TTTGAGGGGT GTATATGCAC ACAGGAGGAT CATGTCTCTG
TGGCTCCTTC CTTTCCATGG TTTCTCCCCT CAACTTACAG ATGCTCTGAC AGCCTCACAC
TGCATCCTCT GACCCATCTG TCCCATAAGA CTGCAGCTTT CTGCCCGAGT TCCAGCTGCC
CTGTACCAAG TAGGCTGCAC AGTGGCCTTG AGGGAATACC TGGAGGACAG TGGCCCTCAC
AGTGCACTGC TTTCCTTCAA GGGTTCAGTT CCTCCAGTTC CCACCTGCTT TTTGTTATTC
TCTAGTGCTA TCAAGTTTTT TTTGTTTTAA ATTATTTTTT TCCAAGTGTA TCATTGTTAT
CTGCAGGAGA GTACATCCAA CAGAAGCTAC TCTACCACTG TGGGAACCGG AGGCTCCTGG
GCCCCACTCT TTATTATGCC ACATGCACAT CCATTTTAAG CCAACAGCCA CACGCACCTC
CACTGTGAGT TCTGTGGCCT
What are genome-wide association studies?
A genome-wide association study is a relatively new technique allowing scientists to identify genes involved in human disease or genetic traits. The genome is searched for small variations, called SNPs that occur more frequently in people with a particular disease or trait than in people without the disease or the trait. Each study may look at hundreds or thousands of SNPs at the same time. The resulting data is used to pinpoint genes that may contribute to a person’s risk of developing a certain disease or the type of hair color.
For more information about genome-wide association studies see: The National Human Genome Research Institute provides more information at: http://www.genome.gov/20019523.
