Gene Deserts in the Human Genome

1
Gene Deserts in the Human Genome
31 of the human genome consists of
intergenic regions larger than 500 Kb.
Centromere
Gene Desert
2
DACH1 A Gene Bracketed by Two Gene Deserts
FLJ22624
DACH
KLH1
876 kb
1,330 kb
430 kb
Over 1,000 human/mouse CNS (Conserved non-coding
sequences)
3
Human-Fugu Sequence Comparison Identifies 13 CNS
Around DACH1
1,500 Kb
DACH
Human-Mouse gt1,000 CNS
Human-Fugu 13 CNS
4
Distant Vertebrate Sequence Comparison of DACH1
CNSs
5
Assaying the CNSs for Enhancer Activity
Transient Transgenics
DACH
LacZ
Hsp68
Stain embryos for LacZ activity
Inject into fertilized eggs
6
DACH gene pattern of expression
Brain / CNS
Eyes
Limbs
7
Dach enchancer 1 Hindbrain
Dachshund
FLJ
140 Kb
8
Dach enhancer 2 Peripheral Nervous System
Dachshund
FLJ
10 Kb
9
-225 Kb
10
Dach enhancer 4 Eyes, CNS, PNS
Dachshund
FLJ
-557 Kb
11
Dach enhancer 5 Limbs
Dachshund
FLJ
-637 Kb
12
Dach enhancer 6 Forebrain
Dachshund
FLJ
-643 Kb
13
-780 Kb
14
Dach2, a Paralog of Dach1 on Chromosome X
Chromosome 13
Dachshund
KLHL1
FLJ
Dachshund2
KLHL4
CHM
Chromosome X

• Same expression Pattern
• Functional Complementation

Duplicated Enhancers?
15
Duplicated Enhancers Shared by Dach1 and Dach2
16
Acknowledgments
LBNL Rubin Lab.

• Eddy Rubin
• Ivan Ovcharenko
• Veena Afzal
• Ingrid Plajzer-Frick
• Michael Collier