Per all sources, his wife's name was Nancy Ann Drusilla Tyler Ann and Nancy were not two different people.
Sources
Sons of the American Revolution Membership Applications, 1889-1970. Louisville, Kentucky: National Society of the Sons of the American Revolution. Microfilm, 508 rolls.
DAR record # A057019
The memorial (54749521) no longer exists on FAG
"Kentucky Marriages, 1785-1979," index, FamilySearch (https://familysearch.org/pal:/MM9.1.1/F474-H4H : accessed 15 Nov 2014), Jesse Holmes and Nancy Tyler, Nov 1803; citing , Shelby, Kentucky, reference ; FHL microfilm 259294
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DNA Connections
It may be possible to confirm family relationships with Jesse by comparing test results with other carriers of his Y-chromosome or his mother's mitochondrial DNA.
However, there are no known yDNA test-takers in his direct paternal line.
Mitochondrial DNA test-takers in the direct maternal line:
Holmes-14 and Holmes-77 appear to represent the same person because: Holmes-14 and Holmes-78 appear to represent the same person because: Same husband of Ann B. Tyler. Great-Grandparents of President Harry S Truman.