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

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

3. 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:

4. Genetic marker typing
LOD > 3 : evidence of linkage

8. Recombination rate Genotype Experiment 1 Experiment 2 A B (n1) 17 3414 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 = 代表完全連鎖
當 θ = 0.5 代表不連鎖

9. 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

10. 108 people: 64 wet earwax; 54 dry earwax

11. More detail study More microsatellite markers Use SNP study
37 SNPs used
rs in ABCC1 exon 4 (538GA, G180R)
rs in LONPL intron 12 (AG)
ss in LONPL intron 14 (A G)

12. 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

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

14. How to determine SNP types?
SNP array

15. Next Generation Screening® microarray with 25,000 features

16. 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

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

18. 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 ( ) in exon 29

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

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

21. Genetics Leads the Bioscience Researches