Chromosomes and Human Genetics Chapter 12

Chromosome Theory of Inheritance Genes have specific locations (loci) on chromosomes. It is the chromosomes that separate and assort independently during meiosis. This explains Mendel’s laws of inheritance.

Karyotype A “picture” of chromosomes arrested in metaphase and sorted by length, centromere location or other defining features Cultured cells are arrested at metaphase by adding colchicine This is when chromosomes are most condensed and easiest to identify Used to help answer questions about an individual’s chromosomes Lets us see sex chromosomes and look for abnormalities in sex chromosomes or autosomes 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 XX (or XY)

Linkage is the tendency of genes located on the same chromosome to be transmitted to­gether in inheritance. Linkage can be disrupted by crossing over—the exchange of parts of homologous chromosomes. Certain alleles that are linked on the same chromosome tend to remain together during meiosis because they are positioned closer together on the chromosome. This eventually led to the generalization that the probability that a cross over will disrupt the linkage of two genes is proportional to the distance that separates them. The careful analysis of recombination patterns in experimental crosses has resulted in linkage mapping of gene locations.

Crossover Frequency Proportional to the distance that separates genes The closer the genes are to each other, the less likely crossing over will occur A B C D Crossing over will disrupt linkage between A and B more often than C and D In-text figure Page 201

Sex Chromosomes Discovered in late 1800s Mammals, fruit flies XX is female, XY is male Butterflies, moths, some birds and some fish XX is male, XY female Human X and Y chromosomes function as homologues during meiosis Differ physically, one is shorter (Y) Differ in the genes they carry

female (XX) male (XY) Sex Determination eggs sperm Male gamete determine sex of offspring in mammals and fruit flies Y X X x XX XY X Y Figure 12.5 Page 198

The Y Chromosome The X Chromosome Fewer than two dozen genes identified One is the master gene for male sex determination SRY gene (sex-determining region of Y) SRY present, testes form SRY absent, ovaries form The X Chromosome Carries more than 2,300 genes Most genes deal with nonsexual traits Genes on X chromosome can be expressed in both males and females

Sex- Linkage homozygous dominant female recessive male Gametes: x X X All F1 have red eyes Gametes: x X X X Y 1/2 1/2 1/4 1/2 1/2 1/4 1/4 F2 generation: 1/4 Figure 12.7 Page 200

X-Linked Recessive Inheritance The characteristics of this condition are: The mutated gene occurs only on the X chromosome. Heterozygous females are phenotypically normal; males are more often affected because the single recessive allele (on the X chromosome) is not masked by a dominant gene. 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.

X-Linked Recessive Inheritance Males show disorder more than females Son cannot inherit disorder from his father Figure 12.12a Page 205

Examples of X-Linked Traits Color blindness Inability to distinguish among some of all colors Hemophilia Blood-clotting disorder 1/7,000 males has allele for hemophilia A Was common in European royal families

Fragile X Syndrome An X-linked recessive disorder Causes mental retardation Mutant allele for gene that specifies a protein required for brain development Allele has repeated segments of DNA

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. Human examples: CF, PKU, Tay Sachs

Autosomal Recessive Inheritance Patterns If parents are both heterozygous, child will have a 25% chance of being affected Figure 12.10a Page 204

Autosomal Dominant Inheritance 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. If one parent is heterozygous and other homozygous recessive, there is a 50 percent chance that any child will be heterozygous. Human examples: Huntingddon’s Disease (nervous system deterioration, death, Symptoms don’t usually show up until person is past age 30, People often pass allele on before they know they have it) and Achondroplasia (a form of dwarfism)

Autosomal Dominant Inheritance Trait typically appears in every generation Figure 12.10b Page 204

Pedigrees A chart of genetic connections among individuals A graphic representation of a families traits Provides data on inheritance patterns through several generations. Knowledge of probability and Mendelian inheritance patterns is used in analysis of pedigrees to yield clues to a trait's genetic basis.

Pedigree Symbols male female marriage/mating offspring in order of birth, from left to right Individual showing trait being studied sex not specified I, II, III, IV... generation Figure 12.9a Page 202

Pedigree for Polydactyly II III IV V female male 5,5 6,6 * 5,5 6,6 6,6 5,5 6,6 5,5 6 7 5,5 6,6 5,5 6,6 5,5 6,6 5,5 6,6 5,6 6,7 12 6,6 6,6 *Gene not expressed in this carrier. Figure 12.9b Page 202

Changes in Chromosome Structure Portions of chromosomes may be lost or rearranged. Results in chromosomal mutations. 4 types: Duplications, deletions, inversions or translocations

Gene sequence that is repeated several to hundreds of times Duplication Gene sequence that is repeated several to hundreds of times normal chromosome one segment repeated three repeats

Inversion A linear stretch of DNA is reversed within the chromosome alters the position and sequence of the genes so that gene order is reversed. segments G, H, I become inverted In-text figure Page 206

Translocation A piece of one chromosome becomes attached to another nonhomologous chromosome a part of one chromosome is transferred to a nonhomologous chromosome Most are reciprocal In-text figure Page 206 one chromosome a nonhomologous chromosome nonreciprocal translocation In-text figure Page 206

Deletion Loss of some segment of a chromosome Most are lethal or cause serious disorder

Changes in Chromosome Number Nondisjunction Failure of chromosomes to separate properly Results in gametes or daughter cells with abnormal number of chromosomes. If a gamete with an extra chromosome (n + 1) joins a normal gamete at fertilization, the diploid cell (zygote )will be 2n + 1; this condition is called trisomy. If an abnormal gamete is missing a (n - 1) joins a normal gamete at fertilization, the diploid cell (zygote )will be 2n – 1; this condition is called monosomy.

nondisjunction at anaphase I chromosome alignments at metaphase I nondisjunction at anaphase I alignments at metaphase II anaphase II Page 208

Aneuploidy Individuals have one extra or less chromosome (2n + 1 or 2n - 1) Major cause of human reproductive failure Most human miscarriages are aneuploids Polyploidy Individuals have three or more of each type of chromosome (3n, 4n) Common in flowering plants Lethal for humans 99% die before birth Newborns die soon after birth

Changes in the Number of Sex Chromosomes Changes in the Number of Autosomes Down Syndrome - Trisomy of chromosome 21 Changes in the Number of Sex Chromosomes Turner Syndrome - females whose cells have only one X chromosome (designated XO). (monosomy) XXX Syndrome Klinefelter Syndrome - Nondisjunction results in an extra X chromosome in the cells (XXY) XYY Condition -Extra Y chromosome in these males (does not affect fertility)

Chi-Square statistical analysis of genetics data X2 = ∑ (o-e)2 e o = observed numbers e = expected numbers Solve the equation Find the degrees of freedom (one less than the total number of choices – types of offspring phenotypes) Look at the critical value table if your answer is less than .05 value, then your results deviate from the expected only from chance If your answer is greater than the .05 value, then your results deviated from the expected for some other reason and you have to figure out why