lecture 4 'segmental duplications as source for genomic innovation: The case of NOTCH2NL'

Question 1

NOTCH signalling

Answer 1

regulates balance between neural stem cells and neuronal differentiation.
To much –> Stemcell renewal
To Less –> leads to premature

Question 2

The NOTCH2NL gene is only seen in the human, not in chimpanzee or macaque. That indicates that NOTCH2NL needs to be emerged in the common ancestor of human, chimp and gorilla. However by looking to a relative coverage map there is seen that there is some conversion of the gene in chimpanzee and in gorilla. So if they don’t have the NOTCH2NL but do show conversion, what is it?

Answer 2

The genes are fusion genes with another gene in front

Question 3

NOTCH2NL

Answer 3

duplication of NOTCH2.
In the humans this NOTCH2 duplications is repaired –> functional NOTCH2NL gene. This NOTCH2NL is also duplicated –> NOTCH2NLA-B-C-D.
In other species this NOTCH2 gene is also duplicated but not functional, it is a fusion gene and contains no promotor. Truncated gene!

Question 4

Function of NOTCH2NL in Human

Answer 4

NOTCH2NL enhancers NOTCH activation, by forming a dimer with NOTCH2, in the presence or absense of canonical ligands. NOTCH2NL leads to less protein and therby delays in cortical differentiation. There is a selective pressure against high NOTCH2NL expression.

Question 5

Expression of NOTCH in NOTCH2NL variants

Answer 5

NOTCH2NLB (ATG) high NOTCH expression
NOTCH2NLA (ATA) low expression
NOTCH2NLC No produced protein

Question 6

Location of NOTCH2NL

Answer 6

NOTCH2NL is located in 1q21.1 which is
associated witch neurological disorders