Androgen Insensitivity Syndrome (AIS) is a human disorder in which an individual's genetic sex (genotype) differs from that individual's observable secondary sex characteristics (phenotypes). A fetus with AIS is genetically male with a 46,XY genotype. The term 46,XY refers to the chromosomes found in most cells of the fetus. Most cells have a total of 46 autosomes, or non-sex chromosomes, and a pair sex chromosomes, XX for genetic females, or XY for genetic males. Due to a defect on the androgen receptor gene (AR) located on the X chromosome, a fetus with AIS cannot process male sex hormones or androgens. The effect on the fetus is that, compared to genetically male fetuses without AIS, it doesn't develop normal male phenotypes. The resistance to androgens affects all of the fetus's organs during embryonic development and during puberty. Although genetically male, persons with AIS can be socially raised as either female or male (sex-of-rearing) yet identify with a gender discordant with their sex-of rearing. AIS and other states of intersexuality challenge physicians, scientists, and society to evaluate definitions of sex.

In humans, sex determination is the process that determines the biological sex of an offspring and, as a result, the sexual characteristics that they will develop. Humans typically develop as either male or female, primarily depending on the combination of sex chromosomes that they inherit from their parents. The human sex chromosomes, called X and Y, are structures in human cells made up of tightly bound deoxyribonucleic acid, or DNA, and proteins. Those are molecules that contain the instructions for the development and functioning of all life forms, including the development of physical traits and body parts that correspond with each biological sex. Humans who inherit two X chromosomes typically develop as females, while humans with one X and one Y chromosome typically develop as males. Sex determination is the beginning of the development of many characteristics that influence how a human looks and functions as well as the societal expectations that other humans have for each other.