1. In a re-sequencing study to detect genetic variation that influences expression and inducibility of cytochrome P450 (CYP) enzymes, novel mutations are detected in the constitutive androstane receptor (CAR; NR1I3), a nuclear hormone receptor that acts as a transcription factor and controls the expression of CYPs including CYP34. Activation of CAR induces (increases) the expression of CYP enzymes.
An alignment of the amino acid sequence of human, monkey, rat, and mouse CARs is indicated below. The amino acid residue positions of interest are indicated by *. 4 8 39 239 * * * *
Human MASREDEFS CEGCKG NFLCGP
Monkey MASREDELS CEGCKG NFLCGP …show more content…
In this case, the two SNPs are in very low LD. They are in very high linkage equilibrium.
4. You have been offering genotyping of a drug-metabolizing enzyme in a medical center in a U.S. city. The patient population is predominantly Caucasian and African-American. The genotyping targets polymorphisms found at the highest frequencies in these two populations. More recently, a high influx of immigrants from South Korea, Japan, and Vietnam begin to enter the city. If you continue to offer the same polymorphisms, what are the major limitations you will encounter in detecting clinically significant genetic variation? How would you modify the genotyping test to address this limitation?
- One of the major limitations that will be observed is that the test might give more negative than positive results for the genetic testing of the Asians. This is because the targeted polymorphisms are more frequently found in Caucasians and African Americans. There might be other polymorphisms for the same gene that are more frequent in the people of Asian descent.
- Another limitation is that since we are only testing for targeted polymorphisms, we cannot capture all the genetic variation for that gene in the
An alignment of the amino acid sequence of human, monkey, rat, and mouse CARs is indicated below. The amino acid residue positions of interest are indicated by *. 4 8 39 239 * * * *
Human MASREDEFS CEGCKG NFLCGP
Monkey MASREDELS CEGCKG NFLCGP …show more content…
In this case, the two SNPs are in very low LD. They are in very high linkage equilibrium.
4. You have been offering genotyping of a drug-metabolizing enzyme in a medical center in a U.S. city. The patient population is predominantly Caucasian and African-American. The genotyping targets polymorphisms found at the highest frequencies in these two populations. More recently, a high influx of immigrants from South Korea, Japan, and Vietnam begin to enter the city. If you continue to offer the same polymorphisms, what are the major limitations you will encounter in detecting clinically significant genetic variation? How would you modify the genotyping test to address this limitation?
- One of the major limitations that will be observed is that the test might give more negative than positive results for the genetic testing of the Asians. This is because the targeted polymorphisms are more frequently found in Caucasians and African Americans. There might be other polymorphisms for the same gene that are more frequent in the people of Asian descent.
- Another limitation is that since we are only testing for targeted polymorphisms, we cannot capture all the genetic variation for that gene in the