Table ED.2 ∣.

Med-PaLM 2 answers to questions about phenotypes albino skin, warfarin metabolism, and aromatic hydrocarbon response.

Candidate Gene Set 4: Albino Skin Input prompt: You are a helpful genetic assistant. The following is a question about genetic discovery. Which of the following genes is most likely associated with phenotype Albino skin. Gene candidates: Grm5, Fzdr, Dlg2, Tyr, Polc4, Sec11a, Ap3b2, Rab38, Tmem135, Cedc81, 17rn6, Fcd, Picalm, Cdc83, Nrs155

Med-PaLM 2 output: The gene most likely associated with the albino skin phenotype is **Tyr**. The Tyr gene encodes the tyrosinase enzyme, which is responsible for the production of melanin. Melanin is the pigment that gives skin, hair, and eyes their color. Mutations in the Tyr gene can lead to a lack of melanin production, resulting in albinism. The other genes listed are not known to be associated with albinism. However, some of them may play a role in other aspects of skin pigmentation. For example, the Grm5 gene is involved in the production of melanocytes, which are the cells that produce melanin. Mutations in the Grm5 gene can lead to a condition called piebaldism, which is characterized by patches of white skin. If you are concerned about a genetic condition, it is important to speak with a doctor or genetic counselor. They can provide you with more information about the condition and its inheritance pattern. They can also order genetic testing to confirm a diagnosis.

Candidate Gene Set 5: Warfarin Metabolism Input prompt: You are a helpful genetic assistant. The following is a question about genetic discovery. Which of the following genes is most likely associated with phenotype Warfarin metabolism. Gene candidates: Igsf8, Kcnj9, Kcnj10, Slc30a1, Icnh1, Masp2, Itpr1, Grin2b, Ctsc, Art5, Trpc2, Rrm1, Adam9, Lpl, Mmp2, Nnmt, Acy1, Gabrg2, Ctsl, Adprtl2, Abhd4, Mmp14, Psmb5, cacna1i, Tmprss2, Sncaip, Aldh7a1, Cyp2c55, Abcc2, Gabre

Med-PaLM 2 output: Out of the genes you listed, the most likely gene associated with warfarin metabolism is **CYP2C9**. This gene encodes an enzyme that is responsible for the metabolism of warfarin. Variations in the CYP2C9 gene can affect how quickly or slowly a person metabolizes warfarin. This can impact the dose of warfarin that a person needs to take in order to achieve the desired effect. Other genes that may be associated with warfarin metabolism include VKORC1, CYP4F2, and CYP2C19. However, CYP2C9 is the most well-studied and has the strongest association with warfarin metabolism. It is important to note that genetic factors are not the only factors that can affect warfarin metabolism. Other factors, such as age, diet, and medications, can also play a role. Therefore, it is important for people taking warfarin to be monitored closely by their healthcare provider. I hope this information is helpful. Please let me know if you have any other questions. Comment: Cyp2c55 is located within a haplotype block that contains murine Cyp29, which is the homolog of human CYP2C29.

Candidate Gene Set 6: Aromatic hydrocarbon response Input prompt: You are a helpful genetic assistant. The following is a question about genetic discovery. Which of the following genes is most likely associated with phenotype Aromatic hydrocarbon response. Gene candidates: Ahr, Dnpep, Dusp2, Vdr, Ren1, Cyp2b19, Pola1, Esr2

Med-PaLM 2 output: The gene most likely associated with the phenotype Aromatic hydrocarbon response is **Ahr**. The Ahr gene encodes the aryl hydrocarbon receptor, which is a transcription factor that regulates the expression of genes involved in the metabolism of aromatic hydrocarbons. Aromatic hydrocarbons are a class of chemicals that are found in many environmental pollutants, such as cigarette smoke and car exhaust fumes. When Ahr is activated by binding to an aromatic hydrocarbon, it can induce the expression of genes that help to detoxify these chemicals. Studies have shown that mutations in the Ahr gene can lead to altered responses to aromatic hydrocarbons. For example, people with certain mutations in the Ahr gene may be more susceptible to the harmful effects of exposure to these chemicals. The other genes listed are not as likely to be associated with the phenotype Aromatic hydrocarbon response. However, some of these genes may play a role in the metabolism of aromatic hydrocarbons or in the response to these chemicals. For example, the Cyp2b19 gene encodes an enzyme that is involved in the metabolism of some aromatic hydrocarbons. Overall, the Ahr gene is the most likely candidate gene for the phenotype Aromatic hydrocarbon response.