The Chromosomal The Chromosomal Basis of InheritanceBasis of Inheritance

Chapter 15Chapter 15

New knowledge confirms Mendel’s New knowledge confirms Mendel’s principles…principles…

► 1890: Cell biologists understand process of meiosis.1890: Cell biologists understand process of meiosis.► 1902: Confirmed that chromosomes are paired in 1902: Confirmed that chromosomes are paired in

diploid cells, and that they separate in meiosis.diploid cells, and that they separate in meiosis.► Biologists develop the Biologists develop the chromosome theory of chromosome theory of

inheritanceinheritance::► • • Mendel’s “factors”, now “genes” are located on Mendel’s “factors”, now “genes” are located on

chromosomes.chromosomes.► • • Chromosomes segregate and independently assort Chromosomes segregate and independently assort

during gamete formation.during gamete formation.► Important work started in 1910 by Thomas Hunt Morgan Important work started in 1910 by Thomas Hunt Morgan

from Columbia University who performed experiments from Columbia University who performed experiments with the fruit fly with the fruit fly Drosophila melanogaster; Drosophila melanogaster; These flies:These flies:

► Are easily cultured in the laboratory (live in small jars; Are easily cultured in the laboratory (live in small jars; can be anesthetized).can be anesthetized).

► Are prolific breeders (100’s of eggs laid).Are prolific breeders (100’s of eggs laid).► Have a short generation time (10 days).Have a short generation time (10 days).► Have only four pairs of chromosomes which are easily Have only four pairs of chromosomes which are easily

seen with a microscope.seen with a microscope.

An exception to Mendel’s An exception to Mendel’s rule…rule…

► Linked genesLinked genes -- Genes located on the same -- Genes located on the same chromosome, which do not indepedently assort and chromosome, which do not indepedently assort and tend to be inherited together.tend to be inherited together.

► B = normal body color b = black body B = normal body color b = black body ► W = normal wing shape w = vestigial wingW = normal wing shape w = vestigial wing► BbWw x bbww BbWw x bbww 1 norm/norm : 1 norm/vest : 1 black/norm : 1 1 norm/norm : 1 norm/vest : 1 black/norm : 1

black/vest (expected)black/vest (expected)► BbWw x bbww BbWw x bbww 5 norm/norm : 1 norm/vest : 1 black/norm : 5 5 norm/norm : 1 norm/vest : 1 black/norm : 5

black/vest (observed)black/vest (observed) ► Sturtevant hypothesized that probability of crossing Sturtevant hypothesized that probability of crossing

over between two genes is directly proportional to the over between two genes is directly proportional to the distance between them.distance between them.

► He used recombination frequencies between genes to He used recombination frequencies between genes to assign them a linear position on a chromosome map.assign them a linear position on a chromosome map.

► One map unit = 1% recombination frequency; genes One map unit = 1% recombination frequency; genes farthest apart have highest recombination frequency.farthest apart have highest recombination frequency.

Discovery of a Sex-Linked GeneDiscovery of a Sex-Linked Gene► Sex-linked genesSex-linked genes -- Genes located on sex chromosomes, -- Genes located on sex chromosomes,

commonly applied only to genes on the X chromosome.commonly applied only to genes on the X chromosome.► Morgan discovered a male fly with white eyes instead of the wild-Morgan discovered a male fly with white eyes instead of the wild-

type red eyes. Morgan mated this mutant white-eyed male with a type red eyes. Morgan mated this mutant white-eyed male with a red-eyed female. red-eyed female.

► ww = white-eye allele= white-eye allele► w+ = red-eye or wild-type allelew+ = red-eye or wild-type allele► P generation: XP generation: Xw+ w+ XXw+w+ x X x Xw w YY► F1 generation: XF1 generation: Xw+w+ X Xww and X and Xw+w+ Y Y (all red-eyed)(all red-eyed)► F2 generation: XF2 generation: Xw+ w+ XXw+w+ and X and Xw+w+ X Xww (all females red-eyed)(all females red-eyed)► XXw+w+ Y and X Y and Xw w Y Y (half males red; half males (half males red; half males

white)white)

► Morgan’s conclusions:Morgan’s conclusions:► If eye color is located only on the X chromosome, then females If eye color is located only on the X chromosome, then females

(XX) carry two copies of the gene, while males (XY) have only one.(XX) carry two copies of the gene, while males (XY) have only one.► Since the mutant allele is recessive, a white-eyed female must Since the mutant allele is recessive, a white-eyed female must

have that allele on both X chromosomes (impossible in this case).have that allele on both X chromosomes (impossible in this case).► A white-eyed male has no wild-type allele to mask the recessive A white-eyed male has no wild-type allele to mask the recessive

mutant allele, so a single copy results in white eyes.mutant allele, so a single copy results in white eyes.

Sex-Linked Disorders in HumansSex-Linked Disorders in Humans► Color blindness, Duchenne muscular dystrophy, Color blindness, Duchenne muscular dystrophy,

hemophilia.hemophilia.► Human X-chromosome is much larger than the Y; Human X-chromosome is much larger than the Y;

more genes on the X, many without a homologous more genes on the X, many without a homologous loci on the Y.loci on the Y.

► Fathers pass X-linked alleles to Fathers pass X-linked alleles to only only and and all all of their of their daughters.daughters.

► Males receive their X chromosome only from their Males receive their X chromosome only from their mothers.mothers.

► Fathers cannot pass X-linked traits to their sons.Fathers cannot pass X-linked traits to their sons.► Mothers can pass X-linked alleles to Mothers can pass X-linked alleles to both both sons and sons and

daughters.daughters.► A female that is heterozygous for the trait can be a A female that is heterozygous for the trait can be a

carrier, carrier, but not show the recessive trait herself; far but not show the recessive trait herself; far more males than females have sex-linked disorders.more males than females have sex-linked disorders.

► Males are said to be Males are said to be hemizygous hemizygous (having only one (having only one copy of a gene in a diploid organism).copy of a gene in a diploid organism).

Sex-Limited/Sex-Influenced Sex-Limited/Sex-Influenced TraitsTraits

►Autosomal traits which affect one Autosomal traits which affect one gender more than the other.gender more than the other.

►A dominant gene causes a rare type A dominant gene causes a rare type of uterine cancer, but only affects of uterine cancer, but only affects women.women.

►A form of baldness also caused by a A form of baldness also caused by a dominant gene usually only affects dominant gene usually only affects men because of hormone levels.men because of hormone levels.

X Inactivation in FemalesX Inactivation in Females► In female mammals, most diploid cells have only In female mammals, most diploid cells have only

one fully functional Xone fully functional X chromosome; one of the 2 chromosome; one of the 2 chromosomes is inactivated during embryonic chromosomes is inactivated during embryonic development.development.

► Inactive X chromosome condenses into an object Inactive X chromosome condenses into an object called a called a Barr bodyBarr body; most Barr body genes are not ; most Barr body genes are not expressed.expressed.

► Barr bodies are highly methylated compared to Barr bodies are highly methylated compared to active DNA; Methyl groups (-CHactive DNA; Methyl groups (-CH33) attach to ) attach to cytosine.cytosine.

► Female mammals are a mosaicFemale mammals are a mosaic of two types of of two types of cells, one with an active X from the father and cells, one with an active X from the father and one with an active X from the mother; one with an active X from the mother; inactivation appears to happen randomly.inactivation appears to happen randomly.

► Examples of this type of mosaicism are coloration Examples of this type of mosaicism are coloration in calico cats.in calico cats.

Humans: Fragile X, muscular Humans: Fragile X, muscular dystrophies, patchy skin dystrophies, patchy skin

discolorationdiscoloration

Genetic Disorders: Alterations of Genetic Disorders: Alterations of Chromosome NumberChromosome Number

► AneuploidyAneuploidy -- having an abnormal number of certain -- having an abnormal number of certain chromosomes.chromosomes.

► Three copies of a chromosome is called “trisomy” (Down’s Three copies of a chromosome is called “trisomy” (Down’s Syndrome, or Trisomy 21); missing a chromosome is Syndrome, or Trisomy 21); missing a chromosome is called “monosomy” (Turner’s Syndrome).called “monosomy” (Turner’s Syndrome).

► PolyploidyPolyploidy -- more than two complete chromosome sets. -- more than two complete chromosome sets.► Triploidy Triploidy means three haploid chromosome sets (3N); may means three haploid chromosome sets (3N); may

be produced by fertilization of an abnormal diploid egg.be produced by fertilization of an abnormal diploid egg.► Tetraploidy Tetraploidy means four haploid chromosome sets (4N); means four haploid chromosome sets (4N);

may result by mitosis without cytokinesis.may result by mitosis without cytokinesis.► Polyploidy is common in plants, but occurs rarely in Polyploidy is common in plants, but occurs rarely in

animals. animals.

► Nondisjunction -- error in meiosis when homologous Nondisjunction -- error in meiosis when homologous chromosomes or sister chromatids fail to separate into chromosomes or sister chromatids fail to separate into different gametes.different gametes.

Genetic Disorders: Alterations of Genetic Disorders: Alterations of Chromosome Number(cont)Chromosome Number(cont)

► Aneuploidy usually prevents normal embryonic Aneuploidy usually prevents normal embryonic development and often results in spontaneous abortion.development and often results in spontaneous abortion.

► Some types cause less severe problems.Some types cause less severe problems.► Down syndrome Down syndrome (1 in 700 live births in U.S.); (1 in 700 live births in U.S.);

characteristic facial features, short stature, heart characteristic facial features, short stature, heart defects, mental retardation.defects, mental retardation.

► Correlates with maternal age; time lag prior to Correlates with maternal age; time lag prior to completion of meiosis at ovulation?completion of meiosis at ovulation?

► Rarer disorders are Rarer disorders are Patau syndrome Patau syndrome (trisomy 13) and (trisomy 13) and Edwards syndrome Edwards syndrome (trisomy 18); incompatable with life.(trisomy 18); incompatable with life.

► Sex chromosome aneuploidy:Sex chromosome aneuploidy:► Klinefelter SyndromeKlinefelter Syndrome (usually XXY); sterile males with (usually XXY); sterile males with

feminine body characteristics.feminine body characteristics.► Extra Y (or “super-male” , Extra Y (or “super-male” , XYY); taller males with higher XYY); taller males with higher

testosterone production.testosterone production.► Turner Syndrome Turner Syndrome (XO); only known viable human (XO); only known viable human

monosomy; short stature; sexual characteristics fail to monosomy; short stature; sexual characteristics fail to develop; sterile.develop; sterile.

Genetic Disorders: Alterations of Genetic Disorders: Alterations of Chromosome StructureChromosome Structure

► Chromosome breakage can alter chromosome Chromosome breakage can alter chromosome structure in four ways:structure in four ways:

► 1. Deletion: loss of a fragment of 1. Deletion: loss of a fragment of chromosome.chromosome.

► 2. Duplication: lost fragment attaches to a 2. Duplication: lost fragment attaches to a homologous chromosome, repeating a homologous chromosome, repeating a sequence. sequence.

► 3. Translocation: lost fragment joins to a 3. Translocation: lost fragment joins to a nonhomologous chromosome.nonhomologous chromosome.

► 4. Inversion: lost fragment reattaches to the 4. Inversion: lost fragment reattaches to the original chromosome in reverse.original chromosome in reverse.

► These errors usually happen during crossing-These errors usually happen during crossing-over.over.

Genetic Disorders: Alterations of Genetic Disorders: Alterations of Chromosome Structure(cont)Chromosome Structure(cont)

► Cri du chat syndrome; Cri du chat syndrome; deletion on chromosome; mental deletion on chromosome; mental retardation, unusual facial features, and cat’s cry.retardation, unusual facial features, and cat’s cry.

► Chronic myelogenous leukemia Chronic myelogenous leukemia (CML); portion of (CML); portion of chromosome 22 switches places with fragment from chromosome 22 switches places with fragment from chromosome 9.chromosome 9.

► Some cases of Some cases of Down syndrome:Down syndrome: the third chromosome the third chromosome 21 translocates to chromosome 15.21 translocates to chromosome 15.

► Prader-Willi syndrome; Prader-Willi syndrome; deletion from the paternal deletion from the paternal chromosome 15; mental retardation, obesity, short chromosome 15; mental retardation, obesity, short stature.stature.

► Angelman syndrome; Angelman syndrome; same deletion from the maternal same deletion from the maternal chromosome 15; uncontrollable spontaneous laughter, chromosome 15; uncontrollable spontaneous laughter, jerky movements, and other mental symptoms.jerky movements, and other mental symptoms.

► Genomic imprintingGenomic imprinting -- changes in chromosomes -- changes in chromosomes inherited from males and females; certain genes inherited from males and females; certain genes expressed differently depending upon whether expressed differently depending upon whether inherited from the ovum or from the sperm cell.inherited from the ovum or from the sperm cell.

Genetic Disorders: Alterations of Genetic Disorders: Alterations of Chromosome Structure(cont)Chromosome Structure(cont)

► Fragile X syndrome Fragile X syndrome (1 in 1500 males; 1 in 2500 (1 in 1500 males; 1 in 2500 females); most common genetic cause of mental females); most common genetic cause of mental retardation.retardation.

► Caused by triplet repeat (CGG); repeated up to 50 Caused by triplet repeat (CGG); repeated up to 50 times on the tip of a normal times on the tip of a normal X X chromosome; chromosome; repeated more than 200 times in a fragile repeated more than 200 times in a fragile X X chromosome.chromosome.

► Syndrome more likely to appear if the abnormal Syndrome more likely to appear if the abnormal X X chromosome is inherited from the mother; chromosome is inherited from the mother; chromosomes in ova are more likely to acquire chromosomes in ova are more likely to acquire new CGG triplets than chromosomes in sperm.new CGG triplets than chromosomes in sperm.

►Maternal imprinting explains why fragile-X disorder Maternal imprinting explains why fragile-X disorder is more common in males. Males (XY) inherit the is more common in males. Males (XY) inherit the fragile fragile X X chromosome only from their mothers.chromosome only from their mothers.

►Heterozygous carrier females are usually only Heterozygous carrier females are usually only mildly retarded.mildly retarded.