Question

Although familial cases of narcolepsy have been reported, most human occurrences are sporadic, and the disorder is generally believed to be multigenic and environmentally influenced (Honda and Matsuki, 1990; Mignot, 1998). In Doberman pinschers, the disorder is transmitted as a single autosomal recessive trait with full penetrance, canarc-1 (Foutz et al., 1979; Baker and Dement, 1985). To unravel the cause of this unique sleep disorder, we undertook the positional cloning of the canine narcolepsy gene. This project led us to identfy a mutation in the gene encoding the receptor for a novel neuropeptide, the hypocretin (orexin) receptor 2 (Hcrtr2), as the cause of canine narcolepsy Let's outline the steps used in this Genetic Analysis! 1. What organism? What phenotype? 2. Collection of mutants: dogs breeders donated them M2 3. Dominance Test: Circle an example of a dominance test on this pedigree M3 4. Complementation testing: Since the phenotypes arose within single dog families, it was reasonable to assume a single gene mutation was responsible for each. So, the authors did not do complementation tests directly. ( imagine that they didn't want to mate dogs from different breeds, but I'm not sure.) But how would they have donea complementation test? F2 Fo. 1. Genetic trees of the Do- berman (a) and Labrador (b) back- crosses. Circle (female) and square (male) symbols show clinical and ca nare-1 status; filled, half-filled, or empty symbols represent, respec- tively, affected, carier, and healthy control canines. GF, grandfather, F father: M, mother. Numbers were se quentially assigned to offspring and are underlined when animals showed spontaneous cataplectic attacks be- fore 5 mo of age. Individuals 06 and 19 were excluded from the study be- cause of uncertain diagnoses. 01 02 03 04 05 06 07 08 09 101 12 13 14 15 16 12 18 19 20 21 22 23 24 25 26 GM 01 02 03 04 0S 06 07 08 09 10 12 13 14 15 16

Answer 1

1: Dogs were used for the testing. Phenotype: All affected with nacrolepsy (homozygous recessive for the gene).
3: Dominance test refer to the cross wherein a F1 hybrid is crossed with recessive parent to decipher its genotype. Attached image encircle the one from the given pedigree.

4: Complementation test could have done by taking affected dogs from different breeds and crossing them. For example: Affected Labrador could have crossed with affected poodle or bull dog.
If the progeny showed normal phenotype with respect to selected disease, the genes responsible for disease in two breeds complemented each other.

個GEE GM Dominace test