Bertram et al. (2005) , NEJM, 352:884-894.

Bertram et al. (2005) , NEJM, 352:884-894.

Bertram et al. (2005) , NEJM, 352:884-894.

Bertram et al. (2005) , NEJM, 352:884-894.

1 2 3 4 5 6 7 8 9 1110

1 2 3 4 5 6 7 9 1110

Transcript Variant 1: All 11 exons

Transcript Variant 2: Exon 8 excluded

Ubiquilin 1 Gene (UBQLN1)

Differential RNA splicing gives twodifferent mRNA variants:

Transcript Variant 2Transcript Variant 1

AD Cases Controls

AD Cases have more mRNA variant 2 than Controls.

Genotype CC(High Risk)

Genotype TC(Medium Risk)

Genotype TT(Low Risk)

The C allele gives more “high risk”mRNA than the T allele

Transcript Variant 2Transcript Variant 1

Conclusion:

•A C/T allele in the intron after exon 8 influences RNA splicing.

•The C allele results in more transcript variant 2 than the T allele.

•The more transcript 2, the greater the risk for Alzheimers.