Identification of mesoderm development (mesd) candidate genes by comparative mapping and genome sequence analysis

Area of Science:

• Genetics
• Developmental Biology
• Comparative Genomics

Background:

• Mouse chromosome 7 harbors critical regions for embryonic development, including mesoderm differentiation (mesd), hypothalamus neuroendocrine lineage (nelg), and liver function (hsdr1).
• Understanding these regions is crucial for identifying genes involved in development and disease.

Purpose of the Study:

• To identify novel genes within the mesd deletion interval on mouse chromosome 7.
• To investigate the functional roles of genes in embryonic development using BAC transgenic approaches.
• To identify conserved homologous regions in the human genome and their association with human diseases.

Main Methods:

• Comparative mapping and genomic sequence analysis to identify novel genes.
• BAC transgenic rescue and complementation to assess gene function and embryonic lethality.
• Human radiation hybrid mapping and BAC contig construction to identify conserved genomic regions.
• Analysis of disease cosegregation with microsatellite markers.

Main Results:

• Four novel genes and Il16 were identified in the mesd deletion interval; mesdc1 and mesdc2 are within the critical mesd region.
• BAC transgenic complementation partially rescued mesd early embryonic lethality, indicating roles for genes outside the critical region.
• A conserved region on human chromosome 15 homologous to mouse mesd, nelg, and hsdr1 regions was identified.
• Three human diseases (ADNFLE, MRST, PAPA) were found to cosegregate with markers in the homologous human region.

Conclusions:

• The study identified novel genes critical for mouse embryonic development and established conserved synteny with human chromosome 15.
• These findings link specific mouse chromosomal regions and their human homologs to developmental processes and human disease.