LD scores and LD-blocks

[@dancerxluv3300440]

Thanks for this great information! Just wanted to leave a note regarding the comment made by the student: From my understanding, LD blocks and TADs are different concepts? LD blocks having more to do with inheritance and likelihood of recombination during a very short time in the cell's life (meiosis) as discussed in the video -- and deduced with LD score info as shown; TADs (topologically associated domains) are related to the small regions/neighborhoods of the genome that have a higher frequency of interactions within the linear DNA and thus regulate gene expression (enahancer-promoter interactions etc.) during interphase/most of the cells life --ideduced using 3C/4C/HiC techniques. Now whether there are mechanisms that make recombination more likely to occur at the bounds of each TAD and thus making LD blocks and TADs line up, so to speak, im not sure! Any thoughts?

[@michelnaslavsky]

Yes, as you described clearly, they are different concepts. The hypothesis of correlation between TAD spans and LD blocks was raised since a plausible interaction between recombination machinery and chromatin condensation could drive such patterns. However, this was not detected: www.ncbi.nlm.nih.gov/pmc/articles/PMC6396425/ . On the other hand, conservation between individuals and across regions of the genome might suggest that certain haplotypes may be enriched (as a result of selection): "One consequence is that entire TADs or sub-TADs do not typically segregate as single haplotypes in human populations, enabling independent selection on regulatory variants versus the promoter and coding variants of their target genes. Furthermore, large LD blocks that span chromatin domain boundaries indicate that regulatory and coding variants from one domain can segregate with variants from the adjacent domain. The fact that haplotype breakpoints do not align with chromatin boundaries may indicate that recombination is deleterious at these functional elements. These findings are different from observations regarding fixed structural differences between genomes of various mammals, which tend to preserve TADs with breakpoints enriched at TAD boundaries (Krefting et al. 2018; Lazar et al. 2018). We therefore conclude that, while chromatin domains are functional genomic entities maintained as syntenic units over evolutionary time, recombination is largely independent of interphase chromatin structure. This creates novel haplotypes of the genomic elements within TADs on which selection can operate."

[@ahlammallak8853]

I love all your videos guys! you are doing an amazing job! Please for next videos focus on the mathematical aspects and the real application using datasets. :D