Researchers at the Icahn School of Medicine at Mount Sinai have made a pivotal breakthrough in understanding the genetic underpinnings of intellectual disability, according to a new study published in Nature Genetics. The discovery of a novel genetic variant associated with intellectual functioning and educational attainment promises to enhance diagnostic precision and open new avenues for targeted therapy.
The research highlights the significant role of tandem repeats -- specific DNA sequences that repeat multiple times on a chromosome -- in impacting intellectual capacities.
"The genome contains a myriad of these tandem repeats that, when expanded, can disrupt the function of genes," lead author Andrew Sharp, a professor of genetics and genomic sciences at Icahn Mount Sinai, said in a news release. "Our research brings to light how these previously underappreciated genetic features can have a profound impact on human intelligence."
Tandem repeats can be likened to duplicated sentences in the genetic "book" of the human genome. When these repeats occur excessively, they can interfere with the genetic instructions essential for development and cognitive abilities.
Using advanced DNA methylation profiling and genotyping techniques, the team pinpointed a repeat expansion of a specific nucleotide sequence within the AFF3 gene, which is strongly linked to educational outcomes. The identified expansion involves a sequence of guanine (G) and cytosine (C) bases (GCC).
This finding could significantly improve the understanding of the genetic basis for at least 0.3 percent of intellectual disability cases, enhancing the accuracy of genetic tests and diagnoses.
"Identifying the AFF3 expansion as a contributor to intellectual disability is a step toward more accurate and timely diagnoses," added Sharp.
The phenome-wide association approach used in the study further emphasizes the broader public health implications of these genetic variations.
Looking ahead, the research team plans to delve deeper into the myriad of tandem repeats present in the human genome, which may reveal further links to various diseases. The study represents an initial yet crucial step into a broader field of genetic research that holds promise for understanding and potentially mitigating intellectual disabilities on a greater scale.