Genes, Chromosomes, and Human Genetics

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Genes, Chromosomes, and Human Genetics

• Chapter 13

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Why It Matters

• Progeria

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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

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Chromosomes

• Genes
• Sequences of nucleotides in DNA
• Arranged linearly in chromosomes

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Linked Genes

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

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Drosophila melanogaster

• Fruit fly
• Model organism for animal genetics
• Compared to Mendels peas
• Used to test linkage and recombination

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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

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Genetic Recombination

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

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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

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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

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Recombination Occurs Often

• Widely separated linked genes often recombine
• Seem to assort independently
• Detected by testing linkage to genes between them

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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

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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

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Sex Chromosomes

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

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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

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Sex Linkage

• Female (XX) 2 copies of X-linked alleles
• Male (XY) 1 copy of X-linked alleles
• Only males have Y-linked alleles

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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

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Eye Color Phenotypes in Drosophila

• Normal wild-type red eye color
• Mutant white eye color

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Human Sex-Linked Genes

• Pedigree chart show genotypes and phenotypes in a
  familys past generations
• X-linked recessive traits more common in males
• Red-green color blindness
• Hemophilia defective blood clotting protein

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Inheritance of Hemophilia

• In descendents of Queen Victoria of England

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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

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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

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Calico Cats

• Heterozygote female (no male calico cats)

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Barr Body

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

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13.3 Chromosomal Alterations That Affect
Inheritance

• Most common chromosomal alterations deletions,
  duplications, translocations, and inversions
• Number of entire chromosomes may also change

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Chromosomal Alterations (1)

• Deletion broken segment lost from chromosome
• Duplication broken segment inserted into
  homologous chromosome

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Chromosomal Alterations (2)

• Translocation broken segment attached to
  nonhomologous chromosome
• Inversion broken segment reattached in reversed
  orientation

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Nondisjunction (1)

• Failure of homologous pair separation during
  Meiosis I

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Nondisjunction (2)

• Failure of chromatid separation during Meiosis II

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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

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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

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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

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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

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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

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Modes of Inheritance

• Autosomal recessive inheritance
• Autosomal dominant inheritance
• X-linked recessive inheritance

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Autosomal Recessive Inheritance

• Males or females carry a recessive allele on an
  autosome
• Heterozygote
• Carrier
• No symptoms
• Homozygote recessive
• Shows symptoms of trait

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Autosomal Dominant Inheritance

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

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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

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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

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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

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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

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Cytoplasmic Inheritance

• Genes carried on DNA in mitochondria or
  chloroplasts
• Cytoplasmic inheritance follows the maternal line
  
• Zygotes cytoplasm originates from egg cell

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Cytoplasmic Inheritance

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

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Cytoplasmic Inheritance

• Inheritance of variegation in Mirabalis

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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