The Dukes family of Orangeburg County, South Carolina, began with Joseph Duke, first documented in the Orangeburg parish records of Rev. John Giessendanner in 1750. His descendants have since spread throughout the world. His parentage has not been proven, although DNA studies have eliminated many possible origins. SNP subclade testing has placed this family in haplogroup J2a4b* (previously known as J2f, J2a1a in the Sengupta et al 2006 nomenclature, or J2a2), which probably arose from a mutation in the vicinity of the Caucasus and spread through maritime contact with areas on the coasts of Crete, western Anatolia, Italy, and Spain.

This large family includes descendants of 17th century Isle of Wight Co VA settler John Duke (often listed as JDIOW). Their haplogroup falls under I, the second most common among persons of European descent. JDIOW may have been the son of William Duke/Ducke who immigrated from England in the late 1630s. He was born around 1640 and died before 1689 with only one known son, John II. Based on a partial will of JDII, he had three grown sons as well as other sons and daughters who were minors. With a descendant of Shadrack Duke testing his Y-DNA and providing records from a family Bible, it seems likely that the members of this group are probably descended from one of three sons of JDII: John III (the Elder), Robert, and William.

This group includes individuals from eastern Henrico County, VA, from Kentucky via Maryland, from North Carolina, Georgia, and Mississippi. They are all thought to trace back to Thomas and Col. Henry Duke. Washington Duke, whose family founded Duke University, is believed to be one of their descendants. Many individuals are believed to be descendants of Capt. Henry Duke of Prince George Co. VA, through his son John Taylor Duke. Three test subjects are from the Henrico Co VA area; one of these test subjects is from a line that includes a Mastin/Maston/Marston Duke in Henrico Co, VA, a name that is documented in the family of Col. Henry Duke. The group also includes three descendants of Squire Staggs Ashley from Orange County, NC, believed to be a Duke descendant who took the Ashley name. The Group 4 haplogroup is under R1b1a1b, which distinguishes them from the IOW Dukes in Group 2 (who may have crossed paths with them in Virginia and North Carolina).

This group includes several families that emigrated from the South Carolina Midlands (Fairfield, Kershaw, Richland and Lexington counties) to Alabama and Mississippi. It also includes the family of John Duke of Lancaster Co SC, whose sons John and Moses Duke went on to Barnwell Co SC, John later immigrating to Tatnall Co GA. This group falls within haplogroup R1b.

There is currently only one individual in this group. He is descended from T. J. Duke of Belfast, Ireland. SNP testing has placed this group in haplogroup T (previously K2), an old lineage found in low frequencies in Africa, Asia and the Middle East, also the haplogroup of the family of Thomas Jefferson. The specific haplotype of the individual in this group is found at low frequency in southern Europe, northern Africa, and the Middle East.