Other Loci

A central question concerning the use of a particular locus to measure chemically induced mutation is whether that particular locus is representative of other loci. The ability of the lymphoblast line HH-4, a WI-L2 subclone, to form colonies in the absence of a feeder layer enabled us to isolate clonal lines that are heterozygous for TK and to develop a mutation assay based on loss of TK. We have also been able to develop an assay based on ouabain (OU) resistance. We have now begun to compare induced mutant frequencies at the tk, hgprt, and Na /K ATPase loci. 

One may compare mutation at the tk locus (FsTdR resistance), at the hgprt locus (6TG resistance), and at the Na /K ATPase locus (OU resistance) via the data in Table 2. While the number of experiments performed to date is small, the mutagens are diverse. In each experiment, mutation for all three markers was measured in the same mutagenized population. 

The marked similarites of mutation at the 6TG and the FaTdR loci do not seem surprising. Both phenotypes seem to involve mutation to inactivate an enzyme responsible for drug intoxication, hypoxanthine-guanine phos-phoribosyltransferase or thymidine kinase. Both of these enzymes have molecular weights near 30,000. 

The induction of OU resistance occurs by a mutation that decreases the binding of OU to the Na /K ATPase but leaves the enzyme functional. As expected for such a restricted mutation, OU resistance is induced at a frequency that is approximately 1% of that for 6TG resistance. We hypothesize that nearly all mutations to OU resistance will be of the base-substitution type. Thus, we conjecture that the ratio of mutation to OU resistance and mutation to 6TG resistance will indicate the relative importance of base substitution to the overall mutation caused by a chemical. The ratio of OU /6TG for the alkylating agent EMS is 6 X 10 , while the ratio for the polycyclic hydrocarbon FA is approximately 4 X 10 . This observation supports the hypothesis that OU is induced only by base substitution. A better test of this hypothesis would compare the mutagenicity of base analogues, such as BUdR, and frameshift mutagens, such as ICR-191. 

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Goate, A.M., Cooper, D.N., Hall, C., Leung, T.K., Solomon, E., Li, L. (1987). Localization of a human heat shock hsp70 gene sequence to chromosome 6 and detection of two other loci by somatic cell hybrid and RFLP analysis. Hum. Gen. 75, 123-128. 

It is possible that in some individuals or some families genes at other loci modify the expression of the galactosemia gene to give normal enzymatic activity in the heterozygote. 

Disease expression may be affected by the action of other loci, termed modifier loci. 

G51, Gene mutation, mouse lymphoma L5178Y cells, all other loci + NT 0.1 Kramers ei al. (1985)... 

The ratio (7-T/7-P) appears to be controlled by a Mendelian factor carried by the second chromosome (Ferveur, 1991). A primary gene was mapped on chromosomal location 2-65.3 and called Ngbo. There are two alleles at this locus, Seychelles and Cameroon, which may act codominantly on the (7-T/7-P) ratio in an either hypomorphic or hypermorphic fashion. These alleles affect the absolute production of 7-P codominantly. However, the production of 7-T seems under polygenic control with epigenetic interactions with Ngbo and other loci on the second and third chromosomes (Ferveur, 1991). 

Other loci also contribute to the risk of schizophrenia as well as other diseases. Mutations in the neuroregulin 1 gene (NRG-1) are also associated with both thought disorders and mood disorders (Green et al., 2005). Abnormalities in the 15ql3-ql4 region of chromosome 15 predispose replicably to the existence of schizophrenia, but also to bipolar disorder, schizoaffective disorder, Prader-Willi syndrome (a developmental disorder associated with psychosis), and some forms of juvenile epilepsy (Leonard and Freedman, 2006). Other loci associated... 

Transformation with cosmid DNA from the Haloferax volcanii minimal set has been used to map 140 ethylmethanesulfonate-induced mutants requiring one of 14 amino acids, uracil, adenine, or guanine. This has added an additional 35 loci to the map, most represented by several mutants in the collection. Some indicate operons, such as the 19 arg mutations mapped to the overlap between cosmids 21 and 247, as well as the neighboring part of cosmid 21. Other loci are likely to contain single genes, such as some of the four unlinked his loci [86]. 

STR and other loci for forensic identity testing loci described in this and later sections below. 

While the HLA loci can be used to study the engraftment of transplanted hematopoietic stem cells (see later in this chapter), other more convenient loci are genotyped for this purpose. These other loci are essential when the transplant donor recipient pair are HLA-identical siblings or allele-matched unrelated individuals. 

Lavedan C, Licamele L, Volpi S, Hamilton J, Heaton C, Mack Ket al (2009) Association of the NPAS3 gene and five other loci with response to the antipsychotic iloperidone identified in a whole genome association study. Mol Psychiatry 14 804-819... 

Susceptibility relates to a mutation in RyR-1, the gene encoding the skeletal muscle ryanodine receptor (RYR-1) other loci have been identified on the L-type Ca + channel and on associated proteins. 

The location of variants and frequencies are also represented in tables that can be downloaded in Microsoft Excel and tab-delimited formats for use in further statistical analyses. Each variant is linked to detailed methods describing the genotyping assay performed. The frequencies of each variant can be displayed according to race or ethnicity, the user can then drill down further to obtain the list of individual subjects who were genotyped at this locus, their characteristics and genotypes at other loci. This information can also be downloaded as an Excel or tab-delimited spreadsheet or exported to run the Phase haplotype determination algorithm (15). 

Actinobacteria (bacteria) F E Temperature 13000 Local thermal adaptation identical 16S sequences but some genetic variation at other loci Hahn and PockI (2005)... 

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