Advanced Genetic Analysis Review - Assignment Example

1 a. There appears to be a synthetic interaction between n1035 and 1367. The disorder is dependent upon several genes and their mutations. 1367 acts hypermorphically, as a synthetic enhancer of the disorder, causing over-expression of the trait. 1035 by comparison acts hypomorphically, by making the biv condition less likely. b. A polygenic disorder, a synthetic interaction increasing likelihood of a mutant condition to a statistical certainty. (100% penetrance) c. There is a negative correlation in penetrance of the bi-vulva mutation when lin-17 and lin-44 are combined. The polygenic factor in this case interacts to diminish likelihood of expression. There appears to be a quantitative locus involved with this trait; In general, polygenic disorders are more rare, and in some cases more difficult to inherit due to this dependency on multiple genetic factors. d. The example of the lin-18 genes when combined with mom-2 suggests that the probability will be less than 10%. Neither of the genes yield probabilities equal to 10%, or even greater than 1%, there is no data that indicates a higher percentage. These mutations are likely to be hypomorphic, as they lower the probability of expression. e. It is probable that during embryonic development, there are two separate stages in which lin-44 and mom-2 are activated leading to a protein that completes a quaternary structure involving the lin-17 and lin-18 membrane proteins. The lack of 44 and mom leads to a protein conformation error resulting in the bi-vulva condition. The available data implies a developmental process in which lin-17 and 18 are transcribed into proteins localized to the membranes; but their natural conformation depends upon the secretory gene-products of lin-44 and mom 2. f. One possible test for this idea would likely be a form of X-ray crystallography to elucidate the structure produced by expression of lin-17 and lin-18, and then to match the structures with the products of 44 and mom. This theory would predict the combination of all these gene products resulting in a single quaternary structure. If no stable structure can be elucidated, or if the secretory products themselves formed a quaternary structure, this would contradict the model. g. A possibility for the function of the hav-1 gene would be a sort of editor/error-correction or chaperone protein mechanism. A mutation in this gene by itself may not produce a reaction; but if combined with another mutation, a defect in hav-1 might result in an inability to modify a defect to the correct conformation; thus acting as a synthetic enhancer making the probability of the bi-vulva mutation a certainty. 2.) a. It is probable that the ability of the DNA segments to rescue the phenotype might signify that the mutant polymorphisms are deletions that lack these particular segments. This is reasonable if insertions of the correct DNA eliminate the mutation, by insertion into the defective sequence. b. Reporter gene mom-2 has a signaling function that effects lin-18, but mom-1 does not, as it does not affect the VPC-4 cell. It is possible that mom-2 assumes control of the maturation process begun in larval stage one by lin-18, and its function is distinct from mom-1. c. VPC-4 is probably a leading, or initiating cell, whose differentiation is structurally vital to the other five, during the maturation process whereby the six cells multiply into a complete structure. VPC-4 It may be a lynchpin in the vulvas development; and its native activity depends on the lin-18 gene. lin-18 triggers cell division in larval stage 1, after which mom-2 is activated to continue this function, as the Anchoring cell triggers the other six cells into further division. The data suggests that the process of differentiation may begin with VPC-4, which activates mom-2 and mom-1 function in a stepwise process. 3.) a. lin-10 -- |lin-18 -- |lin-3 * it is probable that lin-18 is part of a mechanism that suppresses/controls expression of the vulva structure. A mutation of it, depending on polygenic factors causes over-expression; the bi-vulva condition. If lin-18 is functioning, then expression is controlled, and thus a mutation in lin-3 can cancel the formation of the structure - but a lin-18 mutation; resulting in hypermorphic over-expression could render irrelevant lin-3. This apparent cancellation of the effect of lin-3 may be a form of epistasis. 4.) Unc-13 is required by nerves; inserting the gene near the myosin region, which is incorporated into all muscles, had no effect on paralysis for the mutant worms. 5.) a. Sup-6 could be a case of interactional suppression. It does not suppress other alleles - only targeting a paralytic mutation. These types of suppressors can cause a loss of function, against a mutation that adds novel, deleterious function. b. Since the changes occurred in a later generation; the fact that the worms were still fertile was important, meaning that fertility was not affected; allowing for future generations for study of the inheritance patterns of the mutation. c. If UNC-13 is a wild-type, then the suppressor gene has no affinity for it; since sup-6 acts only against the e51 mutation; in the absence of that, wild type UNC-13 should not attract sup-6 at all. IV. d. The products of these 67 other genes should be investigated for their relationship with neuron structure and/or function. Secondarily; correlations between these proteins and muscle/myosin function is a possibility. A gel electrophoresis test-series could be used to organize these proteins collectively by mass, where similarities to nerve or muscle proteins could be quantified. 6.) a. Most likely autosomal recessive; the trait involves carriers over multiple generations, requiring multiple copies of the allele to be expressed phenotypically. X-linked recessive is another possibility; but less likely if a female is also affected. There may be a possibility of epistasis suppressing expression, by masking the effects of another gene. b. In a putative fifth generation, it seems a 100% certainty that offspring will carry the mutational trait; as each parent contains two copies of the allele, which is the only way the trait could be expressed phenotypically; thus there are no other variants possible should they produce children. 7.) In summary, sequencing attempts were made, with data concerning the numbers of genes targeted, and the percentage of targets actually achieved. S2 quantifies the sequences that could be found in either of the two databases; the values diminish towards the later category because of the priority genetic researchers ascribe to deleterious mutations. There will be fewer entirely unknown mutations likely to be harmful as it is a fundamental purpose of genomic research to identify these sequences. As genetic research progresses, unknown disease-causing sequences will become increasingly scarce. This is a probable reason why the number values in the next to last column are lower. 8.) a. Adding the numbers in the columns after the total in S2 still leaves room for more values that do not fit the categories of S2. Extrapolations can then be made concerning the number of nucleotides that comprise a gene, which can then be matched - or not matched to dbSNP. If the average number of sequences in a gene were provided by data, then it would be possible to give a precise estimate of the number of genes. b. There are several possibilities; if children can be affected phenotypically by a heterozygous disorder, it would appear to be autosomal dominant. Since Millers syndrome is autosomal recessive, and if the children do not have the same mutation on the affected chromosome; that could suggest different missense mutations with a different genotype; but essentially the same phenotype. If the mutations are the same, on the affected chromosome, then the children would logically express the trait. But if it were possible for different missense mutations to result in the same phenotype of a disease normally known to be autosomal recessive, it is a reasonable expectation that the copies of the gene would be identical. The affected children in the fourth generation could only be explained by a trait that skips one or more generations. It would require multiple copies of a gene that never expresses phenotypically in the heterozygous condition. c. Millers Syndrome is caused by mutations in the DHODH gene, which encodes for the enzyme dihydroorotate dehydrogenase, this creates a flaw in a biochemical cascade normally responsible for the modification of orotic acid to produce DNA-crucial pyrimidines. Anatomically, this disrupts the natural growth of pharyngeal arches during embryonic development. Read More