Chapter 2 - Single-Gene Inheritance

• In genetics, individual biological properties of a species are referred to as characters or traits.
• There are several different types of analytical approaches to gene discovery, but one widely used method relies on the detection of single-gene inheritance patterns.
• The basic approach of genetics is to compare the properties of variants with the standard and, from these comparisons, to make deductions about genetic function.
• In pedigree analysis, the main clues for identifying an autosomal dominant disorder with Mendelian inheritance are that the phenotype tends to appear in every generation of the pedigree and that affected fathers or mothers transmit the phenotype to both sons and daughters.
• Four patterns of single-gene inheritance are revealed in pedigrees: autosomal recessive disorders, autosomal dominant disorders, X-linked disorders, and mitochondrial disorders.
• The affected phenotype of an autosomal recessive disorder is inherited as a recessive allele; hence, the corresponding unaffected phenotype must be inherited as the corresponding dominant allele.
• Meiosis is preceded by replication and chromosome condensation, but a key difference is that in this case, the two homologous chromosomes pair to form a group of four chromatids at the equatorial plane.
• In the first division of meiosis, the centromere holding a pair of sister chromatids together does not divide.
• At the second division of meiosis, the centromeres divide; and now each chromatid is pulled into its own cell, which is now effectively haploid.
• Meiosis in a diploid heterozygote Aa is shown here: Aa → Aa → 1/2 A and 1/2 a ratio = 1 A : 1 a.
• The 1:1, 3:1, and 1:2:1 ratios in genetics stem from the principle of equal segregation, which states that the haploid products of meiosis from A / a will be 1 2 A and 1 2 a.
• The cellular basis of the equal segregation of alleles is the segregation of homologous chromosomes at meiosis.
• Haploid fungi can be used to show equal segregation at the level of a single meiosis, resulting in a 1:1 ratio in an ascus.
• The molecular basis for chromatid production in meiosis is DNA replication.
• Recessive mutations are generally in genes that are haplosufficient, whereas dominant mutations are often due to gene haploinsufficiency.
• Genes on the X chromosome (X-linked genes) typically have no counterparts on the Y chromosome and show a single-gene inheritance pattern that differs in the two sexes, often resulting in different ratios in the male and female progeny.
• If a known single-gene disorder is present in a pedigree, Mendelian logic can be used to predict the likelihood of children inheriting the disease.
• Mutants are rare compared to wild type, and they arise from wild types by a process called mutation, which results in a heritable change in the DNA of a gene.
• A testcross is the cross of an individual of unknown heterozygosity with a fully recessive parent.
• The recessive individual in a testcross is referred to as a tester.
• The use of a fully recessive tester means that meiosis in the tester parent can be ignored because all of its gametes are recessive and do not contribute to the phenotypes of the progeny.
• An alternative test for heterozygosity is to self the unknown: if the organism being tested is heterozygous, a 3:1 ratio will be found in the progeny.
• Sex chromosomes are present in many animals and plants and segregate equally, but the phenotypic ratios seen in progeny are often different from the autosomal ratios.
• Human sex chromosomes, X and Y, contain different sets of genes.
• The inheritance patterns of genes on the sex chromosomes are different from those of autosomal genes.
• In mammals, the presence of the Y chromosome determines maleness and the absence of a Y determines femaleness.
• Of the species with nonidentical sex chromosomes, a large proportion have an XY system.
• Cytogeneticists divide the X and Y chromosomes into homologous and differential regions.
• The differential regions of the X and Y chromosomes contain most of the genes and are said to be hemizygous.
• The differential region of the X chromosome contains many hundreds of genes, most of which do not take part in sexual function and influence a great range of human properties.
• The Y chromosome contains only a few dozen genes, with some having counterparts on the X chromosome and most taking part in male sexual function.
• One of the genes on the Y chromosome, SRY, determines maleness itself.
• Several other genes on the Y chromosome are specific for sperm production in males.
• The human X and Y chromosomes have two short homologous regions, one at each end, which are called pseudoautosomal regions 1 and 2.
• One or both of these regions pairs with the other chromosome in meiosis and undergoes crossing over.
• In haploids, meiosis takes place at one special stage of the life cycle when two haploid cells unite to form a transient diploid meiocyte.
• Meiocytes form only from the union of cells of different mating types.
• The four haploid cells produced in a single meiosis in haploid organisms, especially fungi, remain together enclosed in a membranous sac, such as an ascus in yeast.
• Mitotic division results in the original chromosome number in each of the two product cells, while meiotic division results in half the original chromosome number in each of the four product cells.
• Population geneticists have been surprised to discover how much polymorphism there is in natural populations of plants and animals generally.