| 1865 | Mendel publishes Laws of Inheritance | Foundation of genetics; patterns directly applicable to Mendelian disorders |
| 1902 | Archibald Garrod describes alkaptonuria as "inborn error of metabolism" | First recognition of inherited biochemical disorders (autosomal recessive) |
| 1910 | Thomas Hunt Morgan discovers sex-linked inheritance in Drosophila | Establishes chromosomal basis of X-linked inheritance; explains haemophilia patterns |
| 1949 | Murray Barr discovers Barr body (inactive X chromosome) | Reveals X-inactivation; explains dosage compensation in XX individuals |
| 1953 | Watson and Crick describe DNA double helix | Molecular basis for point mutations such as sickle cell codon change |
| 1956 | Correct human chromosome number established as 46 | Enables accurate karyotyping for chromosomal disorder diagnosis |
| 1957 | Jérôme Lejeune discovers trisomy 21 causes Down syndrome | First chromosomal cause of a human disorder; opens chromosomal medicine |
| 1958 | Turner syndrome (45, XO) and Klinefelter (47, XXY) karyotypes characterised | Sex chromosome aneuploidies linked to clinical syndromes |
| 1959 | Linus Pauling names sickle cell anaemia the first "molecular disease" | HbS as structural protein variant; point mutation concept established |
| 1990 | Human Genome Project begins | Accelerates gene location mapping; identifies PAH, HBB, F8 chromosomal positions |