Scientists have pinpointed 145 potential "height genes" in cells that make up the cartilage at the ends of children's bones and affect how tall they grow.
These cartilage cells, known as chondrocytes, multiply and mature in areas of tissue called growth plates, which sit near the ends of long bones in children and teens and determine each bone's future length and shape. When a person's growth is complete, these cartilaginous growth plates "close" and are replaced by hard bone. Scientists already knew that chondrocytes play a role in bone growth and human height, but narrowing down which genes control the cells' growth — and, thus, our statures — has proved difficult.
"Pinpointing specific genes associated with human height is a challenging task, as height is a complex trait that is influenced by both genetic and environmental factors," Dr. Nora Renthal, a pediatric endocrinologist at Boston Children's Hospital and Harvard Medical School and senior of the new study, told Live Science in an email. "Our study focused on cartilage cells specifically because they are the primary cell type involved in bone growth."
In a study published Friday (April 14) in the journal Cell Genomics, Renthal and her colleagues screened 600 million mouse cartilage cells to find genes that influence how the cells proliferate and mature. They used CRISPR genome-editing technology to "knock out" candidate genes, which allowed the researchers to observe what happened when these genes were erased and no longer regulated cartilage cells.
Related: What determines a person's height?
The researchers found 145 genes that, when knocked out, triggered abnormal growth and development of mouse cartilage cells. These patterns of abnormal growth were similar to those seen in certain skeletal disorders, such as skeletal dysplasia — a group of genetic disorders that affect the development of bones, joints and cartilage in babies. Those with skeletal dysplasia are typically of short stature and have short limbs, among other symptoms.
Next, the researchers compared these 145 mouse genes with previous results from large-scale genetic studies of human height, called genome-wide association studies (GWAS). In those studies, researchers compared the DNA of thousands of people of different heights to look for gene variants associated with height, Renthal explained. To control for non-genetic factors that influence the trait under study, such as nutrition and disease in the case of human height, these factors are incorporated into GWAS, according to a 2021 review published in the journal Nature Reviews Methods Primers.
"These studies have contributed to our understanding of the genetic basis of complex traits like height by identifying specific genetic regions and genes that are associated with the trait," Renthal said.
The comparison revealed a remarkable overlap between genetic "hotpots" linked to human height in the GWAS and the 145 genes that control cartilage cell growth in mice. This means that these genes, which the researchers have now precisely located in the human genome, could influence height more than other genetic factors do.
"Our current study has helped to identify new genes potentially involved in bone growth and development," Renthal said. "Specific genes and pathways involved in the maturation and proliferation of chondrocytes, the cells that make up cartilage in our bones, play a critical role in human height."
Results from mouse cells may not mirror cellular processes in humans, Renthal noted in a statement, but the researchers think height genes could come in handy in clinical settings.
"It is our hope that the identification of these 145 genes will help patients with skeletal dysplasia and other skeletal disorders," Renthal told Live Science.
