title: Genomic Control of Retinal Cell Number: Challenges, Protocol, and Results.
abstract: This chapter considers some of the challenges in obtaining accurate and consistent estimates of neuronal population size in the mouse retina, in order to identify the genetic control of cell number through QTL mapping and candidate gene analysis. We first discuss a variety of best practices for analyzing large numbers of recombinant inbred strains of mice over the course of a year in order to amass a satisfactory dataset for QTL mapping. We then consider the relative merits of using average cell density versus estimated total cell number as the target trait to be assessed, and why estimates of heritability may differ for these two traits when studying the retina in whole-mount preparations. Using our dataset on cell number for 12 different retinal cell types across the AXB/BXA recombinant inbred strain set as an example, we briefly review the QTL identified and their relationship to one another. Finally, we discuss our strategies for parsing QTL in order to identify prospective candidate genes, and how those candidates may in turn be dissected to identify causal regulatory or coding variants. By identifying the genetic determinants of nerve cell number in this fashion, we can then explore their roles in modulating developmental processes that underlie the formation of the retinal architecture.
authors.affiliation: Neuroscience Research Institute, University of California, Santa Barbara, CA, 93106-5060, USA.|Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, 93106-9625, USA.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Keeley
authors.affiliation: Neuroscience Research Institute, University of California, Santa Barbara, CA, 93106-5060, USA.|Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, 93106-9625, USA.|Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, 02138, USA.
authors.forename: Irene E
authors.initials: IE
authors.lastname: Whitney
authors.affiliation: Neuroscience Research Institute, University of California, Santa Barbara, CA, 93106-5060, USA. breese@psych.ucsb.edu.|Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, 02138, USA. breese@psych.ucsb.edu.|Department of Psychological and Brain Sciences, University of California, Santa Barbara, CA, 93106-9660, USA. breese@psych.ucsb.edu.
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Reese
mesh_terms: D000818:Animals; D002452:Cell Count; D005455:Fluorescent Antibody Technique; D056726:Genetic Association Studies; D023281:Genomics / Q000379:methods; D051379:Mice; D008815:Mice, Inbred Strains; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D011995:Recombination, Genetic; D012160:Retina / Q000166:cytology* / Q000378:metabolism*
keywords: Haplotype; Neuron number; QTL; Recombinant inbred strain; SNP; Variant