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 eyes pr = purple

+ = normal wings vg = 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