TNBGGA: The No Bullshit Guide to Genetic Analysis

The methods of genetic analysis that you have been learning are applicable to to humans. However, we need to combine these genetic principles with an understanding of the physical realities of the human genomeplugin-autotooltip__default plugin-autotooltip_bigGenome: a dataset that contains all DNA information of an organism. Most of the time, this also includes annotation and curation of that information, e.g., the names, locations, and functions of genes within the genome. As an adjective (“genomic”), this usually is used in the context of. To genetics we will add genomics - the study of entire genomesplugin-autotooltip__default plugin-autotooltip_bigGenome: a dataset that contains all DNA information of an organism. Most of the time, this also includes annotation and curation of that information, e.g., the names, locations, and functions of genes within the genome. As an adjective (“genomic”), this usually is used in the context of. Let's revisit an old table we saw in an earlier chapter, with a few additions.

Of course, to many people humans are the organism in which they are most interested, either for their intrinsic interest in themselves or for biomedical applications. Humans are also more difficult to study compared to the other model organisms we have discussed in this book. The human genomeplugin-autotooltip__default plugin-autotooltip_bigGenome: a dataset that contains all DNA information of an organism. Most of the time, this also includes annotation and curation of that information, e.g., the names, locations, and functions of genes within the genome. As an adjective (“genomic”), this usually is used in the context of is much larger and less geneplugin-autotooltip__default plugin-autotooltip_bigGene: read Chapters 02, 03, 04, 05, and 06 for a definition of gene :-) dense than invertebrates such as Drosophilaplugin-autotooltip__default plugin-autotooltip_bigDrosophila melanogaster: a fruit fly species used in genetics research. or C. elegansplugin-autotooltip__default plugin-autotooltip_bigCaenorhabditis elegans: a non-parasitic non-pathogenic nematode species used as a model organism in genetics researhc.. More importantly, we cannot study human genetics by designing experiments using true-breedingplugin-autotooltip__default plugin-autotooltip_bigTrue breeding: a true breeding strain is one that has been inbred for multiple generations. We assume that the vast majority of loci are homozygous in a true breeding strain. mutantsplugin-autotooltip__default plugin-autotooltip_bigMutant: an individual that has a different phenotype than wildtype and likely contains one more mutations that cause this difference. that can generate large quantities of data to test hypotheses prospectively the way we can with model organisms; for ethical reasons we can only study human genetics retrospectively, using whatever meager quantity of data natural human populations provide. Human geneticists therefore rely on non-invasive DNAplugin-autotooltip__default plugin-autotooltip_bigDNA: deoxyribonucleic acid. The genetic material for nearly all life on Earth. tests, genetic mappingplugin-autotooltip__default plugin-autotooltip_bigGenetic mapping: a term describing a variety of different experimental approaches used to determine the physical locations of genes on chromosomes., and statistical analyses to make connections between genotypeplugin-autotooltip__default plugin-autotooltip_bigGenotype: the combination of alleles within an organism or strain. When used as a verb, it means to determine the genotype experimentally. and phenotypeplugin-autotooltip__default plugin-autotooltip_bigPhenotype: an observable feature or property of an organism.. There are, whoever, some advantages to studying human genetics. First, humans are self-screeningplugin-autotooltip__default plugin-autotooltip_bigScreen: a screen is a process through which a researcher looks through a population of individuals in an attempt to find rare individuals with certain phenotypes, usually with no obvious way to enrich for the rare individuals. contrast to a selection.; they will self-report interesting phenotypesplugin-autotooltip__default plugin-autotooltip_bigPhenotype: an observable feature or property of an organism. (usually these are genetic diseases). Second, subtle phenotypesplugin-autotooltip__default plugin-autotooltip_bigPhenotype: an observable feature or property of an organism. may be more recognizable, as affected individuals may be able to communicate directly with researchers.

When we have discussed mappingplugin-autotooltip__default plugin-autotooltip_bigGenetic mapping: a term describing a variety of different experimental approaches used to determine the physical locations of genes on chromosomes. mutationsplugin-autotooltip__default plugin-autotooltip_bigMutation: a change in the DNA of a gene that results in a change of phenotype compared to a reference wildtype allele. See also: mutant. in model organisms, map positions can be described in two ways:

1. You can describe the genetic mapplugin-autotooltip__default plugin-autotooltip_bigGenetic map: a map that shows gene positions on chromosomes measured in centiMorgans. position of a mutationplugin-autotooltip__default plugin-autotooltip_bigMutation: a change in the DNA of a gene that results in a change of phenotype compared to a reference wildtype allele. See also: mutant. relative to other known markerplugin-autotooltip__default plugin-autotooltip_bigMarker: an allele of a gene that provides an easily observable phenotype. Markers are usually cloned or least well mapped. They are used as genetic landmarks in various genetic experiments. In some cases, markers do not have easily observable phenotypes and can only be detected using molecular methods (e.g., SNPs or SSRs). mutationsplugin-autotooltip__default plugin-autotooltip_bigMutation: a change in the DNA of a gene that results in a change of phenotype compared to a reference wildtype allele. See also: mutant., and map distances can be measured using frequency of recombinationplugin-autotooltip__default plugin-autotooltip_bigRecombination: Recombination can have slightly different meanings depending on context:
   
   * In the context of genetic crosses (usually a dihybrid cross or a test cross), recombination refers to the phenomena where the phenotype of the F2 offspring is different than either parent (P generation). $lox$ (i.e., “$white$ is 1.5 m.u. from $yellow$”); or
2. You can describe the physical location of a mutationplugin-autotooltip__default plugin-autotooltip_bigMutation: a change in the DNA of a gene that results in a change of phenotype compared to a reference wildtype allele. See also: mutant. using coordinates on DNAplugin-autotooltip__default plugin-autotooltip_bigDNA: deoxyribonucleic acid. The genetic material for nearly all life on Earth. (i.e., “individuals that are homozygousplugin-autotooltip__default plugin-autotooltip_bigHomozygous: a state for a diploid organism wherein the two alleles for a gene are identical to each other. for a recessiveplugin-autotooltip__default plugin-autotooltip_bigRecessive: used to describe an allele, usually in comparison to wildtype. Recessive alleles do not exhibit their phenotype when combined with a wildtype allele. disease alleleplugin-autotooltip__default plugin-autotooltip_bigAllele: a version of a gene. Alleles of a gene are different if they have differences in their DNA sequence. have a different DNAplugin-autotooltip__default plugin-autotooltip_bigDNA: deoxyribonucleic acid. The genetic material for nearly all life on Earth. sequenceplugin-autotooltip__default plugin-autotooltip_bigSequence: the precise order of monomers in a polymer. In DNA, it refers to the order of G, A, T, and C nucleotides. In RNA, it refers to the order of G, A, U, and C nucleotides. In proteins, it refers to the order of amino acids. at position 3563562 on Chromosomeplugin-autotooltip__default plugin-autotooltip_bigChromosome: a structure that organizes dsDNA in a cell through interactions with various DNA binding proteins. III”).

In human genetics, we don't have visible markerplugin-autotooltip__default plugin-autotooltip_bigMarker: an allele of a gene that provides an easily observable phenotype. Markers are usually cloned or least well mapped. They are used as genetic landmarks in various genetic experiments. In some cases, markers do not have easily observable phenotypes and can only be detected using molecular methods (e.g., SNPs or SSRs). mutationsplugin-autotooltip__default plugin-autotooltip_bigMutation: a change in the DNA of a gene that results in a change of phenotype compared to a reference wildtype allele. See also: mutant. such as “white” and “yellow” in Drosophilaplugin-autotooltip__default plugin-autotooltip_bigDrosophila melanogaster: a fruit fly species used in genetics research., and even if we did we could not force humans to do crosses (and even if we could, we would have to wait 20 years to get an F1 generation!). Instead, we reply on DNAplugin-autotooltip__default plugin-autotooltip_bigDNA: deoxyribonucleic acid. The genetic material for nearly all life on Earth. polymorphisms as markersplugin-autotooltip__default plugin-autotooltip_bigMarker: an allele of a gene that provides an easily observable phenotype. Markers are usually cloned or least well mapped. They are used as genetic landmarks in various genetic experiments. In some cases, markers do not have easily observable phenotypes and can only be detected using molecular methods (e.g., SNPs or SSRs).. A polymorphism is simply a difference in DNAplugin-autotooltip__default plugin-autotooltip_bigDNA: deoxyribonucleic acid. The genetic material for nearly all life on Earth. sequenceplugin-autotooltip__default plugin-autotooltip_bigSequence: the precise order of monomers in a polymer. In DNA, it refers to the order of G, A, T, and C nucleotides. In RNA, it refers to the order of G, A, U, and C nucleotides. In proteins, it refers to the order of amino acids. at a particular location in the genomeplugin-autotooltip__default plugin-autotooltip_bigGenome: a dataset that contains all DNA information of an organism. Most of the time, this also includes annotation and curation of that information, e.g., the names, locations, and functions of genes within the genome. As an adjective (“genomic”), this usually is used in the context of between individuals in a population. These differences can be inside a geneplugin-autotooltip__default plugin-autotooltip_bigGene: read Chapters 02, 03, 04, 05, and 06 for a definition of gene :-), or in between genesplugin-autotooltip__default plugin-autotooltip_bigGene: read Chapters 02, 03, 04, 05, and 06 for a definition of gene :-). DNAplugin-autotooltip__default plugin-autotooltip_bigDNA: deoxyribonucleic acid. The genetic material for nearly all life on Earth. polymorphisms include substitutions, duplications, deletions, etc. Since polymorphisms are defined as differences in DNAplugin-autotooltip__default plugin-autotooltip_bigDNA: deoxyribonucleic acid. The genetic material for nearly all life on Earth. sequenceplugin-autotooltip__default plugin-autotooltip_bigSequence: the precise order of monomers in a polymer. In DNA, it refers to the order of G, A, T, and C nucleotides. In RNA, it refers to the order of G, A, U, and C nucleotides. In proteins, it refers to the order of amino acids. at a specific location, we can use the term locusplugin-autotooltip__default plugin-autotooltip_bigLocus (plural form: loci): a physical location of a gene; often used as a synonym for a gene. to describe or refer to a polymorphism even if it is not part of a geneplugin-autotooltip__default plugin-autotooltip_bigGene: read Chapters 02, 03, 04, 05, and 06 for a definition of gene :-). We can also use alleleplugin-autotooltip__default plugin-autotooltip_bigAllele: a version of a gene. Alleles of a gene are different if they have differences in their DNA sequence. to describe different versions of that locusplugin-autotooltip__default plugin-autotooltip_bigLocus (plural form: loci): a physical location of a gene; often used as a synonym for a gene.. A locusplugin-autotooltip__default plugin-autotooltip_bigLocus (plural form: loci): a physical location of a gene; often used as a synonym for a gene. is said to be polymorphic is two or more allelesplugin-autotooltip__default plugin-autotooltip_bigAllele: a version of a gene. Alleles of a gene are different if they have differences in their DNA sequence. are each present at a frequency of at least 1% in a population.

Two types of DNAplugin-autotooltip__default plugin-autotooltip_bigDNA: deoxyribonucleic acid. The genetic material for nearly all life on Earth. polymorphisms are of particular importance in human genetics: single nucleotideplugin-autotooltip__default plugin-autotooltip_bigNucleotide: molecules that are polymerized to form nucleic acids (DNA or RNA). Includes dNTPs and NTPs. polymorphisms (SNPs) and simple sequenceplugin-autotooltip__default plugin-autotooltip_bigSequence: the precise order of monomers in a polymer. In DNA, it refers to the order of G, A, T, and C nucleotides. In RNA, it refers to the order of G, A, U, and C nucleotides. In proteins, it refers to the order of amino acids. repeats (SSRs; also called microsatellites).