Genes that define the shape of our face

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	rs4648379	TCTGTGGGGCCCTTTGCAACCTCCCT[C/T]ATGCATGAGCAATTCAGGGGTTTGA
PAX3	2q35	rs974448	ACAAATTTTAAAAATTAATTTAAAAA[C/T]TCTGTTCTGTTTAACACTAATAATC
TP63	3q28	rs17447439	CCAGGTGCTCATTTGATGATAGCAGC[A/G]TGAAGCTCTTCCCATTCTGCACCGT
C5orf50	5q35.1	rs6555969	TCCAATCCTCTCATCTGTCCCTCTAA[C/T]GGGCTCCGACAGATCACTCCACAGT
COL17A1	10q24.3	rs805722	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.

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