Medical genetics

Scientists have harnessed powerful data analysis tools and three dimensional studies of genomic geography to implicate new risk genes for osteoporosis, the chronic bone weakening condition that affects millions of people. Knowing the causative genes may later open the door to more effective treatments. “Identifying a disease’s actual underlying cause often helps to steer us toward correct, targeted treatments,” said study leader Struan F.A. Grant, PhD, a director of the Center for Spatial and Functional Genomics at Children’s Hospital of Philadelphia (CHOP).

Research methods

“We have identified two novel genes that affect bone-forming cells relevant to fractures and osteoporosis. Furthermore, the research methods we used could be applied more broadly to other diseases with a genetic component.” Grant and colleagues published their research March 19, 2018 in Nature Communications.

He co-led the study with Andrew D. Wells, PhD, an immunology researcher at CHOP and the other director of the CSFG; and Kurt D. Hankenson, DVM, PhD, an expert in bone formation and remodeling at the University of Michigan. Genetics researcher Alessandra Chesi, PhD, also from CHOP, was the first author, along with three additional joint first authors. Grant and Wells also are faculty members in the Perelman School of Medicine at the University of Pennsylvania.

Association studies

The study team investigate genetic loci, or DNA regions, previously establish to be associate with bone mineral density in genome-wide association studies (GWAS), both in adults and children. “Scientists have known for some time now that the nearest gene to a variant associate with a disease is not necessarily the cause of the disease,” says Wells.

Because GWAS research detects single-base changes in DNA that are usually not located in obvious parts of the genome; much research has turned to the broader context of interactions within the genome- the entire complement of DNA within cells. Sometimes the changes; called single-nucleotide polymorphisms, or SNPs, found in GWAS are located close to a culprit gene.

DNA sequence.

More often the signal comes from a non-coding region of the DNA that regulates another gene that may be thousands of bases away on the DNA sequence. “The geography of the genome is not linear;” said Grant. “Because DNA is fold into chromosomes, parts of the genome may come into physical contact; enabling key biological interactions that affect how a gene is expressed.
That’s why we study the three-dimensional structure of the genome.Because “In analyzing how chromatin; the fibers that make up chromosomes, is arrange into specific shapes; spatial genomics offers insight into how genes physically interact with the regulatory regions in DNA that initiate transcription. Therefore Transcription is the process in which DNA is copy into RNA; the first event in gene expression.