The Chromosomal Basis of Inheritance

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Chapter 15

• The Chromosomal Basis of Inheritance

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Genes are located on chromosomes

• Are located on chromosomes
• Can be visualized using certain techniques

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Mendelian inheritance has its physical basis in
the behavior of chromosomes

• The behavior of chromosomes during meiosis was
  said to account for Mendels laws of segregation
  and independent assortment
• The chromosomal basis of Mendels laws
• Mendelian genes have specific loci on chromosomes
• Chromosomes undergo segregation and independent
  assortment

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Linkage and Crossing Over

• Linkage 2 genes on the same chromosome
• Not Independently Assorted
• Segregate together
• Crossing over
• Linked genes should segregate together
• Crossing over causes them to separate
• Linked genes tend to be inherited together
  because they are located near each other on the
  same chromosome
• Each chromosome
• Has hundreds or thousands of genes

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Homologous Chromosomes
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Expected Frequency
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Linkage and Crossing Over

• Linked genes should always assort together
• Should have resulted in two phenotypes
• Both recessive or both dominant traits
• 50 of each
• Crossing over changes that result
• Result is less clear-cut
• The farther apart genes are on a chromosome
• The more likely they are to be separated during
  crossing over

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Linkage and Crossing Over

• Test cross
• Independent Assortment predicts ¼ of each
  phenotype
• Results are much different
• These genes are linked

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Crossing Over

• Homologous chromosomes line up during meiosis
• Parts of maternal and paternal chromosomes migrate

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Recombinant Offspring

• Recombinant offspring
• Are those that show new combinations of the
  parental traits
• When 50 of all offspring are recombinants
• Geneticists say that there is a 50 frequency of
  recombination

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Linkage Mapping Using Recombination Data

• A genetic map
• Is an ordered list of the genetic loci along a
  particular chromosome
• Can be developed using recombination frequencies

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The Chromosomal Basis of Gender

• Concept 15.3 Sex-linked genes exhibit unique
  patterns of inheritance
• An organisms gender
• Is an inherited phenotypic character determined
  by the presence or absence of certain chromosomes

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The X-Y System

• In humans and other mammals

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Other Systems

• Different systems of sex determination
• Are found in other organisms

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Inheritance of Sex-Linked Genes

• The sex chromosomes
• Have genes for many characters unrelated to sex
• A gene located on either sex chromosome
• Is called a sex-linked gene

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Sex-linked genes follow specific patterns of
inheritance
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Other sex-linked conditions

• Some recessive alleles found on the X chromosome
  in humans cause certain types of disorders
• Color blindness
• Duchenne muscular dystrophy
• Hemophilia

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X inactivation in Female Mammals

• In mammalian females
• One of the two X chromosomes in each cell is
  randomly inactivated during embryonic development

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Tortoise shell cats

• If a female is heterozygous for a particular gene
  located on the X chromosome
• She will be a mosaic for that character

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• Concept 15.4 Alterations of chromosome number or
  structure cause some genetic disorders
• Large-scale chromosomal alterations
• Often lead to spontaneous abortions or cause a
  variety of developmental disorders

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Abnormal Chromosome Number

• When nondisjunction occurs
• Pairs of homologous chromosomes do not separate
  normally during meiosis
• Gametes contain two copies or no copies of a
  particular chromosome
• Large-scale chromosomal alterations
• Often lead to spontaneous abortions or cause a
  variety of developmental disorders

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Nondisjunction
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Aneuploidy

• Aneuploidy
• Results from the fertilization of gametes in
  which nondisjunction occurred
• Is a condition in which offspring have an
  abnormal number of a particular chromosome
• If a zygote is trisomic
• It has three copies of a particular chromosome
• If a zygote is monosomic
• It has only one copy of a particular chromosome

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Polyploidy

• Is a condition in which there are more than two
  complete sets of chromosomes in an organism
• This animal, Tympanoctomys barrerae is tetraploid

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Alterations of Chromosome Structure

• Breakage of a chromosome can lead to four types
  of changes in chromosome structure
• Deletion
• Duplication
• Inversion
• Translocation

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Alterations of chromosome structure
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Human Disorders Due to Chromosomal Alterations

• Alterations of chromosome number and structure
• Are associated with a number of serious human
  disorders

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Down Syndrome

• Is usually the result of an extra chromosome 21,
  trisomy 21

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Aneuploidy of Sex Chromosomes

• Nondisjunction of sex chromosomes
• Produces a variety of aneuploid conditions
• Klinefelter syndrome
• Is the result of an extra chromosome in a male,
  producing XXY individuals
• Turner syndrome
• Is the result of monosomy X, producing an X0
  karyotype

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Disorders Caused by Structurally Altered
Chromosomes

• Cri du chat
• Is a disorder caused by a deletion in a chromosome

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The Philadelphia Chromosome

• Certain cancers
• Are caused by translocations of chromosomes

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Alas, its not that simple

• Concept 15.5 Some inheritance patterns are
  exceptions to the standard chromosome theory
• Two normal exceptions to Mendelian genetics
  include
• Genes located in the nucleus
• Genes located outside the nucleus

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Genomic Imprinting

• In mammals
• The phenotypic effects of certain genes depend on
  which allele is inherited from the mother and
  which is inherited from the father
• Inheritance of igf-2
• Angelman Syndrome/Prader-Willi Syndrome

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Inheritance of igf-2

• Genomic imprinting
• Involves the silencing of certain genes that are
  stamped with an imprint during gamete production

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Angelman Syndrome (the happy puppet

• Ubiquitin protein ligase 3A attaches a small
  protein called ubiquitin to proteins that should
  be degraded.
• Protein degradation is a normal process that
  removes damaged or proteins and maintains the
  normal functions of cells.
• Both copies of the UBE3A gene are active in most
  of the body's tissues. In the brain, only the
  copy inherited from a person's mother is normally
  active

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Inheritance of Organelle Genes

• Extranuclear genes
• Are genes found in organelles in the cytoplasm
• Chloroplasts
• Mitochondria

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Maternal Inheritance Why?

• The inheritance of traits controlled by genes
  present in the chloroplasts or mitochondria
• Depends solely on the maternal parent because the
  zygotes cytoplasm comes from the egg

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Mitochondrial Inheritance

• Some diseases affecting the muscular and nervous
  systems
• Are caused by defects in mitochondrial genes that
  prevent cells from making enough ATP

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THE END
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Morgans Experimental Evidence Scientific Inquiry

• Thomas Hunt Morgan
• Provided convincing evidence that chromosomes are
  the location of Mendels heritable factors

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Morgans Choice of Experimental Organism

• Morgan worked with fruit flies
• Because they breed at a high rate
• A new generation can be bred every two weeks
• They have only four pairs of chromosomes

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• Morgan first observed and noted
• Wild type, or normal, phenotypes that were common
  in the fly populations
• Traits alternative to the wild type
• Are called mutant phenotypes

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Correlating Behavior of a Genes Alleles with
Behavior of a Chromosome Pair

• In one experiment Morgan mated male flies with
  white eyes (mutant) with female flies with red
  eyes (wild type)
• The F1 generation all had red eyes
• The F2 generation showed the 31 redwhite eye
  ratio, but only males had white eyes

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• Morgan determined
• That the white-eye mutant allele must be located
  on the X chromosome

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• Morgans discovery that transmission of the X
  chromosome in fruit flies correlates with
  inheritance of the eye-color trait
• Was the first solid evidence indicating that a
  specific gene is associated with a specific
  chromosome

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How Linkage Affects Inheritance Scientific
Inquiry

• Morgan did other experiments with fruit flies
• To see how linkage affects the inheritance of two
  different characters

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• Morgan crossed flies
• That differed in traits of two different
  characters

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• Morgan determined that
• Genes that are close together on the same
  chromosome are linked and do not assort
  independently
• Unlinked genes are either on separate chromosomes
  of are far apart on the same chromosome and
  assort independently

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Genetic Recombination and Linkage
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Recombination of Unlinked Genes Independent
Assortment of Chromosomes

• When Mendel followed the inheritance of two
  characters
• He observed that some offspring have combinations
  of traits that do not match either parent in the
  P generation

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Recombination of Linked Genes Crossing Over

• Morgan discovered that genes can be linked
• But due to the appearance of recombinant
  phenotypes, the linkage appeared incomplete

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• Morgan proposed that
• Some process must occasionally break the physical
  connection between genes on the same chromosome
• Crossing over of homologous chromosomes was the
  mechanism

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• A linkage map
• Is the actual map of a chromosome based on
  recombination frequencies

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• Many fruit fly genes
• Were mapped initially using recombination
  frequencies

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Linked genes - Exhibit recombination frequencies
less than 50
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Epigenetics

• http//www.pbs.org/wgbh/nova/sciencenow/3411/02.ht
  ml
• Mol Cell Biol. 1998 November 18(11) 67676776.
• Characterization of Novel Parent-Specific
  Epigenetic Modifications Upstream of the
  Imprinted Mouse H19 Gene
• Piroska E. Szabó, Gerd P. Pfeifer, and Jeffrey R.
  Mann
• Division of Biology, Beckman Research Institute
  of the City of Hope, Duarte, California 91010
• Abstract Genomic imprinting results in
  parent-specific monoallelic expression of a small
  number of genes in mammals. The identity of
  imprints is unknown, but much evidence points to
  a role for DNA methylation. The maternal alleles
  of the imprinted H19 gene are active and
  hypomethylated the paternal alleles are inactive
  and hypermethylated. Roles for other epigenetic
  modifications are suggested by allele-specific
  differences in nuclease hypersensitivity at
  particular sites. To further analyze the possible
  epigenetic mechanisms determining monoallelic
  expression of H19, we have conducted in vivo
  dimethylsulfate and DNase I footprinting of
  regions upstream of the coding sequence in
  parthenogenetic and androgenetic embryonic stem
  cells. These cells carry only maternally and
  paternally derived alleles, respectively. We
  observed the presence of maternal-allele-specific
  dimethylsulfate and DNase I footprints at the
  promoter indicative of protein-DNA interactions
  at a CCAAT box and at binding sites for
  transcription factors Sp1 and AP-2. Also, at the
  boundary of a region further upstream for which
  existent differential methylation has been
  suggested to constitute an imprint, we observed a
  number of strand-specific dimethylsulfate
  reactivity differences specific to the maternal
  allele, along with an unusual chromatin structure
  in that both strands of maternally derived DNA
  were strongly hypersensitive to DNase I cutting
  over a distance of 100 nucleotides. We therefore
  reveal the existence of novel parent-specific
  epigenetic modifications, which in addition to
  DNA methylation, could constitute imprints or
  maintain monoallelic expression of H19.

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Epigenetics

• What is the official name of the UBE3A gene?
• The official name of this gene is ubiquitin
  protein ligase E3A (human papilloma virus
  E6-associated protein, Angelman syndrome).
• UBE3A is the gene's official symbol. The UBE3A
  gene is also known by other names, listed below.
• What is the normal function of the UBE3A gene?
• The UBE3A gene provides instructions for making
  an enzyme called ubiquitin protein ligase E3A.
  This enzyme is involved in targeting proteins to
  be broken down (degraded) within cells. For
  example, the p53 protein, which controls cell
  growth and division, is one of the targets of
  ubiquitin protein ligase E3A. Protein degradation
  is a normal process that removes damaged or
  unnecessary proteins and helps maintain the
  normal functions of cells.
• Ubiquitin protein ligase 3A attaches a small
  protein called ubiquitin to proteins that should
  be degraded. Cellular structures called
  proteasomes recognize and digest proteins tagged
  with ubiquitin.
• Both copies of the UBE3A gene are active in most
  of the body's tissues. In the brain, however,
  only the copy inherited from a person's mother
  (the maternal copy) is normally active. This
  parent-specific gene activation is known as
  genomic imprinting.
• http//ghr.nlm.nih.gov/geneube3a

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Epigenetics AS Chromosome 15

• Mechanisms causing Angelman syndrome.
• deletion 15q11-q13
• 2. paternal UPD- uniparental disomy
• 3. IC (imprinting center) mutation
• 4. UBE3A mutation.