Exploring a Putative Gene גיא וקסמן רועי נבון

Problem definition Taking one of the thousands of Putative genes that were “found” In the human genome project & Trying to determine whether this Sequence might be a real gene that can be translated into a protein product.

The Selected Gene: NM_014727 Homo sapiens myeloid/lymphoid or mixed-lineage leukemia 4 (MLL4).

PSI-BLAST

The Locus problem Many entrances are actually on the same locus (SNPs, flanking, different Alleles etc`).

Different Entrances on the Same Chromosomal Region

Conserved Domains CXXC zinc finger SET1 Zinc finger

2-BLAST 2-BLAST between the putative MLL4 gene & the most similar real Gene-Trithorax, from Drosophila Melanogaster. E=5e-87 E=2e-82

Multiple Alignment SET1 domain

3D Structure – Zinc Finger Domain

Biological Aspects Drosophila melanogaster ככה נראיתי פעם... The trithorax gene, a trans-acting regulator of the bithorax complex in Drosophila, encodes a protein with zinc-binding domains. Mazo AM, Huang DH, Mozer BA, Dawid IB ככה נראיתי פעם...

Homo Sapians Acute mixed-lineage leukemia t(4;11)(q21;q23) generates an MLL-AF4 fusion product

Conclusions 1. We found a high similarity between our putative gene and genes from other species. 2. The MLL4 putative gene contains at least 3 conserved domains. 3. The homologue genes from Drosophila and Human are associated with the nervous system and leukemia respectively.

Possible directions for future research 1. Trying to find DNA motifs which bind to our putative gene and to its homologues. 2. Trying to isolate the full length protein. 3. When 3D structure prediction will be available, we’ll try to compare our putative protein with other known proteins.