The Genetic of Earwax Wet earwax is a dominant allele! Petrakis et. al (1967) Science 158, p1992

World wild distribution of earwax types Open: dry type Dark: wet type Yoshiura (2006) Nat. Genetics

Earwax type linked to a disease? Japanese Case Report: A Paroxysmal kinesigenic choreoathetosis, (PKC, 陣發性運動障礙性疾病) patient who told that six people in her family also had choreoathetosis, and that those with the disease had wet earwax. Wet earwax is rare in Japan and PKC is rare, too! The cause of PKC is still unknown but seem linked to chromosome 16 near centremere Swoboda, et al. Neurology 2000;50:224-30.

Genetic marker typing LOD > 3 : evidence of linkage

Recombination rate Genotype Experiment 1 Experiment 2 A B (n1) 17 34 14 28 A b (n3) 8 16 A B (n4) 11 22 Total 50 100 總樣品數 互換率 θ 範圍 [0, 0.5] 當 θ = 0 代表完全連鎖 當 θ = 0.5 代表不連鎖

LOD score logarithm (base 10) of odds Developed by Newton E. Morton NR: non recombination; R: recombination LOD score > 3.0: evidence for linkage. (A score of 3.0 means the likelihood of observing the given pedigree if the two loci are not linked is less than 1 in 1000). LOD score < -2.0: evidence to exclude linkage

108 people: 64 wet earwax; 54 dry earwax

More detail study More microsatellite markers Use SNP study 37 SNPs used rs17822931 in ABCC1 exon 4 (538GA, G180R) rs6500380 in LONPL intron 12 (AG) ss49784070 in LONPL intron 14 (A G)

SNP Single nucleotide polymorphism (SNP, pronounced snip) Within a population, SNPs can be assigned a minor allele frequency (>1%) may fall within coding sequences of genes, non-coding regions of genes, or in the intergenic regions between genes synonymous or nonsynonymous Missense or nonsense

How to find out new SNP? Sequencing SSCP (single strand conformation polymorphism)

How to determine SNP types? SNP array

Next Generation Screening® microarray with 25,000 features

Genotyping of three SNPs Dry earwax (63/64): AA-AA-AA Dry earwax (1/64): GA-GA-GA Wet earwax (6/54): GG-GG-GG Wet earwax (33/54): GA-GA-GA Wet earwax (15/54): AA-AA-AA Only two haplotypes in Japan; Phenotype - genotype inconsistency

Do more case study New series of 126 cases Dry type (87/88): AA homozygotes Wet type (38/38) GA or GG Only rs17822931 is nonsynonymous Dry type is recessive

What happened to 1/88? A allele to dry type, G allele to wet type One exception is dry type with GA allele Sequence the gene of ABCC11 G allele had a 27-bp deletion (3939-3965) in exon 29

What is the function ABCC11? Multidrug resistance-associated protein 8 (MRP8) Rs17822931 G180R

Effect of SNP rs17822931 Dry type: A allele  G180R: Low activity in cGMP transport  Low lipophiles secretion

Genetics Leads the Bioscience Researches