Before the appearance of chromosomal mapping techniques, many genes had already been mapped to the sex chromosome. This favored status of the sex chromosome was thanks to the convenience with which sex-linked traits may be determined through pedigree analyses. On the opposite hand, determining which of the 22 autosomes a non-sex-linked gene mapped to presented researchers with a completely new set of challenges. Nonetheless, pedigree analyses continued to be a useful tool for autosomal gene mapping. By following cosegregating phenotypes in pedigrees, researchers were able to generate linkage maps of the 22 human autosomes.

Perhaps the foremost significant advance in mapping human autosomes occurred in 1968, when Donahue et al. published the primary report describing the assignment of a gene to somebody's autosome. More specifically, Donahue and colleagues demonstrated that the Duffy blood type locus (called Fy), the key component of blood type heterozygosity, mapped to human chromosome 1.

The gene located at the Duffy people locus encodes a transmembrane receptor found on the surface of red blood cells. Two common alleles of the Fy gene (called Fya and Fyb) exist, and that they produce kinds of the receptor that differ only within the organic compound at position 43. The Fya allele was first discovered in 1950, supported the observation that a hemophiliac patient named Duffy, who had received numerous blood transfusions, developed antibodies against the Fya protein. The Fyb allele was then discovered one year later in an exceedingly woman who had born to several children. The Fya and Fyb alleles were determined to be codominant, which implies that homozygous and heterozygous individuals is readily identified through an easy biopsy.

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