Pedigree Analysis in Human Genetics Chp.4 Human Pedigrees

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Pedigree Analysis in Human Genetics Chp.4 Human
Pedigrees

• The use of pedigrees is an important method for
  analyzing the inheritance of traits in human
  populations

Fig. 4-CO, p. 70
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4.1 Pedigree Analysis and Construction is a Basic
Method in Human Genetics

• Analysis of pedigrees using knowledge of
  Mendelian principles allows us to
• Determine whether the trait has a dominant or
  recessive pattern of inheritance
• Determine whether the gene in question is located
  on an X or Y chromosome or on an autosome
• This kind of information can be used to predict
  risk

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Patterns of Inheritance

• Patterns in the pedigree are used to determine
  how a trait is inherited
• Autosomal dominant
• Autosomal recessive
• X-linked dominant
• X-linked recessive
• Y-linked
• Mitochondrial inheritance

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Keep In Mind

• Pedigree construction and analysis are basic
  methods in human genetics

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Pedigree Analysis

• Pedigree analysis proceeds in several steps
• Rule out patterns of inheritance that are
  inconsistent with the pedigree
• If only one pattern of inheritance is consistent
  with the pedigree, it is accepted as the pattern
  for that trait
• If more than one pattern in consistent with the
  pedigree, which one is expected to be more
  likely?
• If due to small sample size, it is impossible to
  choose among pattern of inheritance, the
  inclusion of more family members may be necessary

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4.2 Autosomal Recessive Traits

• Characteristics of autosomal recessive traits
• For rare traits, most affected individuals have
  unaffected parents
• All children of affected parents are affected
• The risk of an affected child with heterozygous
  parents is 25
• The trait is expressed in both males and females

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Pedigree A Rare Autosomal Recessive Trait
Fig. 4-2, p. 73
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Example of an Autosomal Recessive Trait Cystic
Fibrosis

• Cystic fibrosis A fatal recessive genetic
  disorder associated with abnormal secretions of
  the exocrine glands

Fig. 4-3a, p. 75
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The Frequency of the Gene for Cystic Fibrosis in
the Human Population

• 1 in 25 Americans of European descent
• 1 in 46 Americans of Hispanic descent
• 1 in 65 African Americans
• 1 in 250 Asian Americans

Fig. 4-4, p. 75
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Cystic Fibrosis Gene Product (CTRF)

• The CFTR gene was identified in 1989
• CFTR protein controls the movement of chloride
  ions across the plasma membrane

Fig. 4-5, p. 76
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Exploring GeneticsWas Noah an Albino?

• Noahs flesh was white as snow
• From the Book of Enoch the Prophet
• Phenotype Lack of pigmentation
• Inheritance of albinism
• An autosomal recessive trait
• Normal, heterozygous parents (may be closely
  related)
• Homozygous recessive offspring (albino)

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4.3 Autosomal Dominant Traits

• Characteristics of autosomal dominant traits
• Heterozygotes have an abnormal phenotype
• Every affected individual has at least one
  affected parent (except in traits with high
  mutation rates)
• If an affected individual is heterozygous and has
  an unaffected mate, each child has a 50 chance
  of being affected
• Two affected individuals can have an unaffected
  child
• Usually an affected family member in each
  generation

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Pedigree An Autosomal Dominant Trait
Fig. 4-6, p. 77
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Example of an Autosomal Dominant Trait Marfan
Syndrome

• Marfan syndrome
• An autosomal dominant genetic disorder that
  affects the skeletal system, cardiovascular
  system, and eyes
• Individuals are tall, thin, long arms and legs.
  Thin fingers
• Heart defects

Fig. 4-7, p. 77
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Cardiovascular Effects of Marfan Syndrome

• Marfan syndrome weakens connective tissue around
  the base of the aorta

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4.4 Sex Linked Inheritance

• Genes on sex chromosomes have a distinct pattern
  of inheritance
• Males (XY) pass their X chromosome to all of
  their daughters but none of their sons
• Females (XX) pass an X chromosome to all of their
  children
• Most genes on the X chromosome are not on the Y
  chromosome
• Males carrying an X-linked recessive allele
  express the recessive phenotype

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Distribution of Sex Chromosomes from Generation
to Generation
Fig. 4-10, p. 79
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Sex Linked Traits

• X-linked
• Pattern of inheritance that results from genes
  located on the X chromosome
• Y-linked
• Pattern of inheritance that results from genes
  located only on the Y chromosome

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In Males, Genes on the X chromosome Hemizygous

• Hemizygous
• A gene present on the X chromosome that is
  expressed in males in both the recessive and
  dominant condition

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X-Linked Dominant Traits

• Quite rare inheritance pattern
• Affected males produce all affected daughters and
  no affected sons
• A heterozygous affected female will transmit the
  trait to half of her children
• Sons and daughters are equally affected
• On average, twice as many daughters as sons are
  affected

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Pedigree of an X-linked Dominant Trait
Fig. 4-11, p. 79
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X-Linked Recessive Traits

• X-linked recessive traits affect males more than
  females because males are hemizygous for genes on
  the X chromosome

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X-Linked Recessive Inheritance

• Affected males receive the mutant X-linked allele
  from their mother and transmit it to all of their
  daughters, but not to their sons
• Daughters of affected males are usually
  heterozygous
• Sons of heterozygous females have a 50 chance of
  being affected
• Hemizygous males (only one X) and females
  homozygous for the allele are affected

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Pedigree X-Linked Recessive Inheritance
Fig. 4-12, p. 80
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Example of an X-linked Recessive Trait Color
Blindness

• Color blindness
• Defective color vision caused by reduction or
  absence of visual pigments
• Three forms red, green, and blue blindness
• About 8 of the male population in the US
  affected

Fig. 4-13, p. 80
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Testing For Color Blindness

• People with normal color vision see the number 29
  in the chart those who are color-blind cannot
  see the number

Fig. 4-14, p. 81
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Color Blindness Defect in the Retina

• Defects in photoreceptor cells of the retina
  (cone cells) cause color blindness

Fig. 4-15, p. 81
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Example of an X-linked Recessive Trait Muscular
Dystrophy

• Muscular dystrophy
• A group of genetic diseases associated with
  progressive degeneration of muscle tissue
• Duchenne and Becker muscular dystrophy are
  inherited as X-linked recessive traits
• Duchenne muscular dystrophy (DMD) affects 1 in
  3,500 males in the US

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Molecular Characteristics ofDuchenne Muscular
Dystrophy

• Dystrophin proteins are flexible and that
  normally stabilize the muscle cells during
  contraction are defective
• Plasma membranes are torn apart during muscle
  contraction, causing death of muscle tissue

Fig. 4-16, p. 82
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4.5 Paternal Inheritance Y Chromosome

• Only males have Y chromosomes
• Genes on the Y chromosome are passed directly
  from father to son
• All Y-linked genes are expressed
• Males are hemizygous for genes on the Y
  chromosome
• To date only 36 Y-linked traits have been
  identified

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Pedigree Y-Linked Traits
Fig. 4-18, p. 84
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4.6 Non-Mendelian Maternal Inheritance
Mitochondrial Genes

• Mitochondria
• Cytoplasmic organelles that convert energy from
  food into ATP (ATP powers cellular functions)
• Carry DNA for 37 mitochondrial genes
• Genetic disorders in mitochondrial DNA are
  associated with defects in energy conversion

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Mitochondrial Inheritance

• Mitochondria (and genetic disorders caused by
  mutations in mitochondrial genes) are maternally
  inherited
• Mitochondria are transmitted from mothers to all
  their offspring through the cytoplasm of the egg

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Pedigree Mitochondrial Inheritance
Fig. 4-19, p. 84
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Exploring GeneticsHemophilia and History

• Queen Victoria passed the X-linked recessive gene
  for hemophilia to several of her children

p. 85
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4.7 An Online Catalog of Human Genetic Traits

• OMIM
• Genetic traits are described, cataloged, and
  numbered in a database called Online Mendelian
  Inheritance in Man
• OMIM is updated daily and contains information
  about all known human genetic traits
• Each trait is assigned an OMIM number
• There are more that 10,000 entries

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4.8 Many Factors can Affect the Pattern of
Inheritance

• Variations in gene expression affect pedigree
  analysis and assignment of genotypes to members
  of the pedigree
• Several factors can affect gene expression
• Interactions with other genes in the genotype
• Interactions between genes and the environment

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4.8 Many Factors can Affect the Pattern of
Inheritance

• Phenotypes are often age related
• Example Huntington disease
• Penetrance and expressivity cause variations in
  phenotype
• Penetrance the probability the the phenotype
  will appear
• Expressivity The range of phenotypes from a
  given genotype

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An Example of Incomplete Penetrance and Variable
Expression

• Camptodactyly
• A dominant trait (immobile, bent little fingers)
  with variable expression

Fig. 4-22, p. 88
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Keep In Mind

• Patterns of gene expression can be influenced by
  many different environmental factors

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Common recessive alleles can produce pedigrees
that resemble dominant inheritance

• Common alleles can enter a pedigree from outside
  the family and thus appear dominant

Fig. 4-23, p. 88