Genes, Chromosomes, and Human Genetics Chapter 13

Why It Matters  Progeria

13.1 Genetic Linkage and Recombination  The principles of linkage and recombination were determined with Drosophila  Recombination frequency can be used to map chromosomes  Widely separated linked genes assort independently

Chromosomes  Genes Sequences of nucleotides in DNA Arranged linearly in chromosomes

Linked Genes  Genes carried on the same chromosome Linked during transmission from parent to offspring Inherited like single genes Recombination can break linkage

Drosophila melanogaster  Fruit fly Model organism for animal genetics Compared to Mendel’s peas Used to test linkage and recombination

Gene Symbolism  Normal alleles (wild-type) Usually most common allele Designated by “+” symbol Usually dominant Wild-type Mutant + = red eyespr = purple + = normal wingsvg = vestigial wings

Genetic Recombination  Alleles linked on same chromosome exchange segments between homologous chromosomes  Exchanges occur while homologous chromosomes pair during prophase I of meiosis

Recombination Frequency  Amount of recombination between two genes reflects the distance between them  The greater the distance, the greater the recombination frequency Greater chance of crossover between genes

Chromosome Maps  Recombination frequencies used to determine relative locations on a chromosome  Linkage map for genes a, b, and c:  1 map unit = 1% recombination = 1 centimorgan

Recombination Occurs Often  Widely separated linked genes often recombine Seem to assort independently Detected by testing linkage to genes between them

13.2 Sex-Linked Genes  In both humans and fruit flies, females are XX, males are XY  Human sex determination depends on the Y chromosome

13.2 (cont.)  Sex-linked genes were first discovered in Drosophila  Sex-linked genes in humans are inherited as they are in Drosophila  Inactivation of one X chromosome evens out gene effects in mammalian females

Sex Chromosomes  Sex chromosomes determine gender X and Y chromosomes in many species XX: female XY: male  Other chromosomes are called autosomes

Human Sex Chromosomes  Human X chromosome Large (2,350 genes) Many X-linked genes are nonsexual traits  Human Y chromosome Small (few genes) Very few match genes on X chromosome Contains SRY gene Regulates expression of genes that trigger male development

Sex Linkage  Female (XX): 2 copies of X-linked alleles  Male (XY): 1 copy of X-linked alleles  Only males have Y-linked alleles

Sex Linkage  Males have only one X chromosome One copy of a recessive allele results in expression of the trait  Females have two X chromosomes Heterozygote: recessive allele hidden (carrier) Homozygote recessive: trait expressed

Eye Color Phenotypes in Drosophila  Normal wild-type: red eye color  Mutant: white eye color

Human Sex-Linked Genes  Pedigree chart show genotypes and phenotypes in a family’s past generations  X-linked recessive traits more common in males Red-green color blindness Hemophilia: defective blood clotting protein

Inheritance of Hemophilia  In descendents of Queen Victoria of England

X Inactivation (1)  Dosage compensation In female mammals, inactivation of one X chromosome makes the dosage of X-linked genes the same as males  Occurs during embryonic development

X Inactivation (2)  Random inactivation of either X chromosome  Same X chromosome inactivated in all descendents of a cell  Results in patches of cells with different active X chromosomes

Calico Cats  Heterozygote female (no male calico cats)

Barr Body  Tightly coiled condensed X chromosome  Attached to side of nucleus  Copied during mitosis but always remains inactive

13.3 Chromosomal Alterations That Affect Inheritance  Most common chromosomal alterations: deletions, duplications, translocations, and inversions  Number of entire chromosomes may also change

Chromosomal Alterations (1)  Deletion: broken segment lost from chromosome  Duplication: broken segment inserted into homologous chromosome

Chromosomal Alterations (2)  Translocation: broken segment attached to nonhomologous chromosome  Inversion: broken segment reattached in reversed orientation

Nondisjunction (1)  Failure of homologous pair separation during Meiosis I

Nondisjunction (2)  Failure of chromatid separation during Meiosis II

Changes in Chromosome Number  Euploids Normal number of chromosomes  Aneuploids Extra or missing chromosomes  Polyploids Extra sets of chromosomes (triploids, tetraploids) Spindle fails during mitosis

Aneuploids  Abnormalities usually prevent embryo development  Exception in humans is Down syndrome Three copies of chromosome 21 (trisomy 21) Physical and learning difficulties Frequency of nondisjunction increases as women age

Polyploids  Common in plants Polyploids often hardier and more successful Source of variability in plant evolution  Uncommon in animals Usually has lethal effects during embryonic development

13.4 Human Genetics and Genetic Counseling  In autosomal recessive inheritance, heterozygotes are carriers and homozygous recessives are affected by the trait  In autosomal dominant inheritance, only homozygous recessives are unaffected

13.4 (cont.)  Males are more likely to be affected by X-linked recessive traits  Human genetic disorders can be predicted, and many can be treated

Modes of Inheritance  Autosomal recessive inheritance  Autosomal dominant inheritance  X-linked recessive inheritance

Autosomal Recessive Inheritance  Males or females carry a recessive allele on an autosome  Heterozygote Carrier No symptoms  Homozygote recessive Shows symptoms of trait

Autosomal Dominant Inheritance  Dominant gene is carried on an autosome  Homozygote dominant or heterozygote Show symptoms of the trait  Homozygote recessive Normal

X-Linked Recessive Inheritance  Recessive allele carried on X chromosome  Males Recessive allele on X chromosome Show symptoms  Females Heterozygous carriers, no symptoms Homozygous, show symptoms

Genetic Counseling  Identification of parental genotypes Construction of family pedigrees Prenatal diagnosis  Allows prospective parents to reach an informed decision about having a child or continuing a pregnancy

Genetic Counseling Techniques  Prenatal diagnosis tests cells for mutant alleles or chromosomal alterations  Cells obtained from: Embryo Amniotic fluid around embryo (amniocentesis) Placenta (chorionic villus sampling)  Postnatal genetic screening Biochemical and molecular tests

13.5 Nontraditional Patterns of Inheritance  Cytoplasmic inheritance follows the pattern of inheritance of mitochondria or chloroplasts  In genomic imprinting, the allele inherited from one of the parents is expressed while the other allele is silent

Cytoplasmic Inheritance  Genes carried on DNA in mitochondria or chloroplasts  Cytoplasmic inheritance follows the maternal line Zygote’s cytoplasm originates from egg cell

Cytoplasmic Inheritance  Mutant alleles in organelle DNA Mendelian inheritance not followed (no segregation by meiosis) Uniparental inheritance from female

Cytoplasmic Inheritance  Inheritance of variegation in Mirabalis

Genomic Imprinting  Expression of an allele is determined by the parent that contributed it Only one allele (from either father or mother) is expressed  Other allele is turned off (silenced) Often, result of methylation of region adjacent to gene responsible for trait