Chapter 12 Chromosome Variations and Human Genetics
I. Too Young to Be Old
A. Because of a rare defect in an autosomal dominant gene, persons suffering from progeria syndrome will age a lifetime in the first decade of life.
B. The analysis of human inheritance is a fascinating but often baffling field of study.

II. Chromosomal Theory of Inheritance
A. Return of the Pea Plant
1. By 1882, Walther Flemming had observed threadlike chromosomes in the nuclei of dividing cells.
2. By 1887, August Weismann had suggested that meiosis halves the number of chromosomes when gametes are made.
3. By 1900, Mendel’s work was finally appreciated, namely his view that diploid cells have two units for each trait and the units segregate during gamete formation.
B. Autosomes and Sex Chromosomes
1. Most of the chromosomes are of the same quantity and type in both sexes and are called autosomes (44 in humans).
2. Sex chromosomes determine gender.
a. Human females have two X chromosomes; males have one X and one Y.
b. Each human egg will contain twenty-two autosomes plus one X; but sperm will carry twenty-two autosomes plus either an X or a Y.
c. The Y chromosome carries the gene for TDF (testis determining factor).
3. Chromosomes are visualized in a lab preparation called a karyotype.
4. Nonsexual traits are also coded for on the sex chromosomes.
C. Linkage and Crossing Over
1. Linkage is the tendency of genes located on the same chromosome to be transmitted together in inheritance.
2. Linkage can be disrupted by crossing over.
a. Crossing over is an exchange of parts of homologous chromosomes.
b. The probability that crossing over will lead to the separation of two genes on a chromosome is proportional to the distance between them; that is, the farther apart two genes are, the greater their frequency of crossing over.
3. Crossing over introduces variations in genotypes and phenotypes and provides for the selection process necessary to evolution.

III. Chromosome Variations in Humans
A. Human genetics is difficult to study.
1. We live under variable conditions in diverse environments.
2. Humans mate by chance and may, or may not, choose to reproduce.
3. Humans live as long as those who study them.
4. The small family size characteristic of human beings is not sufficient for meaningful statistical analysis.
B. The analysis of family pedigrees provides data on inheritance patterns through several generations.
1. Abnormality is a term applied to a genetic condition that is a deviation from the usual, or average, and is not life-threatening.
2. Disorder is more appropriately used to describe conditions that cause medical problems.
C. Autosomal Recessive Inheritance
1. The characteristics of this condition are:
a. Either parent can carry the recessive allele on an autosome.
b. Heterozygotes are symptom-free; homozygotes are affected.
c. 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.
D. Autosomal Dominant Inheritance
1. A dominant allele is 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. Achondroplasia (dwarfism) is a benign abnormality, but Huntington’s disorder is serious degeneration of the nervous system with an onset from age 40 onward.
E. X-Linked Recessive Inheritance
1. The characteristics of this condition are:
a. The mutated gene occurs only on the X chromosome.
b. Heterozygous females are phenotypically normal; males are affected because they have only one allele for the trait (on the X chromosome) and it can be recessive.
c. A normal male mated with a female heterozygote have 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, the inability of the blood to clot because the genes do not code for the necessary clotting agent(s).
F. Changes in Chromosome Structure
1. A deletion is the loss of a chromosome segment.
a. A deletion happens when a terminal segment is lost, or when viruses, chemicals, or irradiation cause breaks in a chromosome region.
b. For example, the loss of a portion of chromosome 5 causes a disorder called cri-du-chat with its symptoms of crying and mental retardation.
2. Duplication occurs when a gene sequence is in excess of the normal amount; apparently this is true of chromosome regions that code for polypeptides of hemoglobin.
3. An inversion alters the position and sequence of the genes so that gene order is reversed.
4. A translocation occurs when a part of one chromosome is transferred to a nonhomologous chromosome.
a. It is seen in some forms of cancer such as when a segment of chromosome 8 has been transferred to chromosome 14.
b. It may result in the fusion of two nonhomologous chromosomes, reducing the chromosome number.
G. Changes in Chromosome Number
1. Categories of Change
a. Aneuploidy is a condition in which the gametes or cells of an affected individual end up with one extra or one less chromosome than is normal.
b. Polyploidy is the presence of three or more of each type of chromosome in gametes or cells. It is common in plants but fatal in humans.
2. Mechanisms of Change
a. Tetraploid germ cells can result if cytoplasmic division does not follow normal DNA replication and mitosis.
b. 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.
3. Down Syndrome
a. Down syndrome results from trisomy 21; 1 in 1,000 liveborns in North America are affected.
b. Most children with Down syndrome show mental retardation, and 40 percent have heart defects.
c. Down syndrome occurs more frequently in children born to older women.
4. Turner Syndrome
a. Turner syndrome involves females whose cells have only one X chromosome (designated XO).
b. Affected individuals are sterile and have other phenotypic problems such as premature aging and shorter life expectancy.
5. Klinefelter Syndrome
a. Nondisjunction results in an extra X chromosome in the cells (XXY) of these affected males.
b. Mental retardation and sterility are symptoms.
6. XYY Condition
a. The extra Y chromosome in these males does not affect fertility, but they are taller than average and are slightly mentally retarded.
b. Erroneous correlations have linked these persons with predisposition to crime.