Between 1953 and 1957, before the Meselson-Stahl experiment verified semi-conservative replication of DNA, scientists debated how DNA replicated. In 1953, James Watson and Francis Crick proposed that DNA was composed of two helical strands that wound together in a coil. Their model suggested a replication mechanism, later termed semi-conservative replication, in which parental DNA strands separated and served as templates for the replication of new daughter strands. Many scientists, beginning with Max Delbrück, questioned Watson and Cricks’ model and suggested new theories for DNA replication. By 1957, three theories about DNA replication prevailed: semi-conservative, conservative, and dispersive replication. Then, Matthew Meselson and Franklin Stahl conducted the Meselson-Stahl experiment, which returned results that supported the semi-conservative theory of DNA replication. The collaboration among scientists that ultimately produced concrete evidence of the DNA replication mechanism furthered both theoretical and physical explanations of genetics and molecular biology, providing insight into how life develops, reproduces, and evolves.

Rosalind Elsie Franklin worked with X-ray crystallography at King's College London, UK, and she helped determine the helical structure of DNA in the early 1950s. Franklin's research helped establish molecular genetics, a field that investigates how heredity works on the molecular level. The discovery of the structure of DNA also made future research possible into the molecular basis of embryonic development, genetic disorders, and gene manipulation.

Y-chromosomes exist in the body cells of many kinds of male animals. Found in the nucleus of most living animal cells, the X and Y-chromosomes are condensed structures made of DNA wrapped around proteins called histones. The individual histones bunch into groups that the coiled DNA wraps around called a nucleosome, which are roughly 10 nano-meters (nm) across. The histones bunch together to form a helical fiber (30 nm) that spins into a supercoil (200 nm). During much of a cell's life, DNA exists in the 200 nm supercoil phase.

A genome-wide association study, or GWAS, is a method for identifying variations in DNA that may contribute to the development of a particular trait, such as a disease. A GWAS relies on identifying statistical correlations between many, often thousands of, DNA markers and a particular trait. Scientists employ GWASs to try to identify the genetic contributions to complex traits, such as common human diseases. Complex traits are ones that scientists suspect are the result of multiple genes and environmental inputs acting together, in contrast to simple, Mendelian disorders that result primarily from the disturbance of a single gene. The genetic variants identified through a GWAS typically account for only a small proportion of the expected genetic contribution to a complex trait, which scientists refer to as the missing heritability problem. Since 2006, scientists have conducted thousands of GWASs aimed at identifying the genetic contributions to complex traits and have identified many thousands of genetic variations that correlate with those traits, although as of 2025, because of the missing heritability problem and other limitations, the concrete contributions of GWASs to medicine have so far been modest.