Chromosomes and Human Genetics

  1. The Chromosomal Basis of Inheritance–An Overview
    1. Genes and Their Chromosome Locations
      1. Genes are units of information about heritable traits.
      2. Diploid organisms possess pairs of homologous chromosomes, which are alike in length, shape, and gene sequence.
      3. Alleles are slightly different molecular forms of the same gene, which are shuffled during meiosis.
      4. Crossing over between homologous chromosomes results in genetic recombination.
      5. A chromosome’s structure may change due to deletion, duplication, inversion, or translocation.
    2. Autosomes and Sex Chromosomes
      1. Sex chromosomes (23) determine gender.
        1. Human females XX
        2. Males XY.
      2. Most of the chromosomes are of the same quantity and type in both sexes and are called autosomes (44 in humans).
    3. Karyotype Analysis
      1. Chromosomes are visualized in a lab preparation called a karyotype.
      2. Each chromosome has distinct size, length, centromere location, and banding (staining) patterns.

  2. Sex Determination in Humans
    1. The Y chromosome carries a male-determining gene that leads to formation of male organs and tissues
      1. Primary male sexual characteristics (form in the embryo from 4-10 weeks): testes, vas deferens, glans penis, prostate gland, cowpers gland…)
      2. Secondary male sexual characteristics (develop at puberty in response to androgenic hormonal signals): Facial hair, deepened voice, pubic hair, production of semen…)
    2. Absence of the male chromosome in females results in formation of female organs and tissues.
      1. Primary sexual characteristics (form in the embryo from 4-10 weeks) (Ovaries, uterine tubes, uterus, vaginal canal, labia, mammary glands…)
      2. Secondary female sexual characteristics (develop at puberty in response to estrogenic hormonal signals): Adipose deposition in the breast tissue and hips, pubic hair, menarche, widening of hips…)
    3. The X chromosome obviously codes for sexual traits, but it also carries many genes for non-sexual traits.
    4. "Sex" and "gender" are concepts are merely semantic delineations. Some variations in genotype or phenotype can result in sexual ambiguity. These conditions are surprisingly common. Sometimes, only genetic screening can identify the condition.
  3. Recombination Patterns and Chromosome Mapping
    1. Crossing Over and Genetic Recombination
      1. Linkage is the tendency of genes located on the same chromosome to be transmitted together in inheritance. Linkage can be disrupted by crossing over.
        1. Crossing over is an exchange of parts of homologous chromosomes.
      2. This eventually led to the generalization that the probability of crossing over will disrupt the linkage of two genes is proportional to the distance that separates them.
    2. Linkage Mapping (Lab 3)
      1. The careful analysis of recombination patterns in experimental crosses has resulted in linkage mapping of gene locations.
      2. Linkage maps do not show the actual distances between genes but rather gives the map distance that can then be correlated with the physical distance.
  4. Human Genetic Analysis
    1. Constructing Pedigrees
      1. A pedigree is a chart that shows genetic connections among individuals.
      2. The analysis of family pedigrees provides data on inheritance patterns through several generations.
      3. Knowledge of probability and Mendelian inheritance patterns is used in analysis of pedigrees to yield clues to a trait’s genetic basis.
  5. Patterns of Autosomal Inheritance
    1. Autosomal Recessive Inheritance
      1. The characteristics of this condition are:
        1. Either parent can carry the recessive allele on an autosome.
        2. Heterozygotes are symptom-free; homozygotes are affected.
        3. Two heterozygous parents have a 50 percent chance of producing heterozygous children and a 25 percent chance of producing a homozygous recessive child. When both parents are homozygous, all children can be affected.
      2. Galactosemia (the inability to metabolize lactose) is an example of autosomal recessive inheritance in which a single gene mutation prevents manufacture of an enzyme needed in the conversion pathway. Tay-Sachs is another example.
    2. Autosomal Dominant Inheritance
      1. The dominant allele is nearly always expressed and if it reduces the chance of surviving or reproducing, its frequency should decrease; mutations, nonreproductive effects, and postreproductive onset work against this hypothesis.
      2. If one parent is heterozygous and other homozygous recessive, there is a 50 percent chance that any child will be heterozygous.
      3. Huntington disorder is serious degeneration of the nervous system with an onset from age 40 onward, by which time the gene has (usually) been passed to offspring unknowingly.
      4. Achondroplasia (dwarfism) is a benign abnormality that does not affect persons to the point that reproduction is impossible so the gene is passed on.
  6. Patterns of X-Linked Inheritance
    1. X-Linked Recessive Inheritance
      1. The characteristics of this condition are:
        1. The mutated gene occurs only on the X chromosome.
        2. Heterozygous females are phenotypically normal; males are more often affected because a dominant gene does not mask the single recessive allele (on the X chromosome).
        3. A normal male mated with a female heterozygote has a 50 percent chance of producing carrier daughters and a 50 percent chance of producing affected sons. In the case of a homozygous recessive female and a normal male, all daughters will be carriers and all sons affected.
      2. A serious X-linked recessive condition is hemophilia A, (affects 1/7,000 males), which is the inability of the blood to clot because the genes do not code for the necessary clotting agent(s).
      3. Duchenne muscular dystrophy is a serious failure of the muscles with an early onset leading to death by the early twenties.
    2. X-Linked Dominant Inheritance
      1. The inheritance pattern is similar to that for X-linked recessive alleles, except it is expressed in heterozygous females, albeit rarely.
      2. In faulty enamel trait the enamel coating of the teeth fails to develop properly.
  7. Changes in Chromosome Number
    1. Categories and Mechanisms of Change
      1. Aneuploidy - Changes by the addition or loss of a single chromosome. (-somy)
        1. Normally as a result of nondisjunction in meiosis II or I.
      2. Euploidy - changes by the addition or loss of entire genomes. (-ploidy) (common in plants but fatal in humans)
        1. A chromosome number can change during mitotic or meiotic cell division or during the fertilization process.
        2. Tetraploid germ cells can result if cytoplasmic division does not follow normal DNA replication and mitosis.
      3. Nondisjunction at anaphase I or anaphase II frequently results in a change in chromosome number.
        1. If a gamete with an extra chromosome (n + 1) joins a normal gamete at fertilization, the diploid cell will be 2n + 1; this condition is called trisomy.
        2. If an abnormal gamete is missing a chromosome, the zygote will be 2n -1, monosomy.
    2. Changes in the Number of Autosomes
      1. Down syndrome results from trisomy 21; 1 in 1,100 liveborns in North America are affected.
      2. Most children with Down syndrome show mental retardation, and 40 percent have heart defects.
      3. Down syndrome occurs more frequently in children born to women over age 35.
    3. Changes in the Number of Sex Chromosomes
      1. XO condition (Turner Syndrome)
        1. Turner syndrome involves females whose cells have only one X chromosome (designated XO).
        2. Affected individuals (1/2,500 to 10,000 girls) are infertile and have other phenotypic problems such as premature aging and shorter life expectancy.
        3. About 75 percent of the cases are due to nondisjunction in the father; furthermore, about 98 percent of all XO zygotes spontaneously abort.
      2. XXY Condition (Klinefelter Syndrome)
        1. Nondisjunction results in an extra X chromosome in the cells (XXY) of these affected males (1/500 to 2,000 liveborn males).
        2. About 67 percent of these result from nondisjunction in the mother, 33 percent in the father.
        3. Slight mental retardation, sterility, and body feminization are symptoms.
      3. XYY Condition (Supermale syndrome)
        1. The extra Y chromosome in these males (1/1,000) does not affect fertility, but they are taller than average and are slightly mentally retarded.
        2. Erroneous correlations have linked these persons with predisposition to crime.
    4. Other genetic changes that result in sexual ambiguity
      1. Point Mutations (next unit)
        1. SRY mutations
        2. TFS (androgen receptor deficiency)
        3. Alpha-5 reductase deficiency