Human Pedigree and Genetic Disease

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Human Pedigree and Genetic Disease
Gregor Mendel
Thomas Bayes
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Common Pedigree Symbols
Male
Marriage
Female
Sex Unknown
Consanguineous Marriage
Affected Female
No Known Pregnancy
Female Carrier of Sex-linked Recessive
Unmarried
Female Carrier (Heterozygous)
Divorce and Remarried
Dead
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Common Pedigree Symbols
Pregnancy in Progress
Dizygotic (nonidentical, fraternal) twins
Three Males
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Five Individuals (both sexes)
Monozygotic (identical) twins
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Spontaneous Abortion
Adopted Child
Proband, propositus, or index case
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Famous Kid
Happy new wife!
Bad Divorce
Triplets!
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Mistakes in Meiosis

• Chromosomes fail to separate properly during
  meiosis, i.e., nondisjunction

• ANEUPLOIDY -- an abnormal number of chromosomes

• Examples

• Downs Syndrome (Trisomy-21)

• Klinefelters Syndrome

• Turners Syndrome

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Polygenic Inheritance

• Most human characteristics are polygenic, meaning
  they are influenced by several genes, e.g. skin
  color influenced by 3-6 genes also, eye color,
  height, hair color
• Complex characters are those that are influenced
  strongly by both the environment and genes, e.g.,
  diabetes, heart disease, stroke, skin color,
  height

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More patterns of inheritance..

• Multiple alleles - genes with three or more
  alleles, e.g., ABO blood groups
• Incomplete dominance condition that results in
  a display of a trait that is intermediate between
  the two parents
• X-linked traits determined by x-linked genes,
  e.g., color blindness
• Sex-influenced traits usually autosomal, e.g.
  baldness is influenced by testosterone
• Single-allele traits more than 200 human traits
  are governed by single dominant alleles, e.g.,
  Huntingtons disease

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Detecting Genetic Disease

• Genetic Screening examination of a persons
  genetic makeup involving karyotypes, blood tests
  for certain proteins, or direct tests of DNA
• 200 genetic disorders can be detected in the
  fetus
• Amniocentesis removal of amniotic fluid from
  the sac that surrounds the fetus between the 14th
  and 16th week of pregnancy
• Chorionic villi sampling sample of cells
  derived between the 8th and 10th week from the
  zygote - cells grow between the mothers uterus
  and the placenta cells chromosomes, and proteins
  analyzed

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Detecting Genetic Disease

• Chorionic villi sampling CVS can help identify
  chromosomal problems such as Down syndrome or
  other genetic diseases such as cystic fibrosis,
  Tay-Sachs disease and sickle cell anemia. CVS is
  considered to be 98 accurate in the diagnosis of
  chromosomal defects, such as Down syndrome.

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Normal Female Karyotype
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Normal Male Karyotype
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Downs Syndrome

• Smallest chromosomes with 1500 genes affected.

• Occurs in 1 out of every 800 babies.
• 40 congenital heart defects.

• Can result from maternal age or chromosome defect.

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Klinefelters Syndrome

• Occurs in one out of every 1000 males.

• Results from extra X chromosome XXY.

• Males tall, sterile, small testicles, and
  mentally handicapped.

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Turners Syndrome

• Occurs in females.

• Results from XO condition.

• Female is short, sterile, and mentally impaired.

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Single Gene Inheritance
Pedigree Analysis

• Autosomal dominant traits
• Huntingtons Disease on chromosome 4
• Marfan Syndrome on chromosome 15
• Breast Cancer on chromosomes 17

• Autosomal recessive traits
• Tay-Sachs Disease on chromosome 15
• Cystic Fibrosis on chromosome 7
• Sickle Cell Anemia on chromosome 11

• X-Linked Disease (Sex-Linked)
• Hemophilia --Duchennes muscular dystrophy
• Color Blindness

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Autosomal Dominant Traits

• Present on any autosomal chromosome, i.e., 1-22.

• One allele present disease present, i.e., a
  person has it or he or she does not

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Huntingtons Disease

• Begins to show up by age 45-55, within 10-20
  years, death is eminent.

• Progressive degeneration of nervous system
  irregular body movements and slurred speech.

• If one parent has HD, offspring have 50 chance
  of inheriting disease.

• Autosomal dominant on chromosome 4 1 in 10,000
  births

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Huntingtons Disease
Hh
hh
What are the genotypes of the parents?
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Marfan Syndrome

• Symptoms long limbs, loose joints, deformed
  vertebral column, crowded teeth, rupture of large
  arteries
• 1 in 20,000 Americans born with it
• Caused by lack of fibrillin-1, a major component
  of connective tissue found in ligaments and
  blood-vessel sheaths

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Autosomal Recessive

• Disease manifests itself if offspring inherits
  one recessive gene from each parent.

• If parents are carriers, 25 of offspring will
  have disease.

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Tay-Sachs Disease

• 1 in 600 Jews of European descent born with it

• Lipids deposited in nervous system, causing brain
  to be damaged -- blindness, loss of movement,
  mental deterioration.
• No break down of cellular wastes in lysosome due
  to absence of hexosaminidase A mutation causes
  nerve death

• Symptoms appear around 6 months of age and
  victims die due to paralysis and/or convulsions
  before the age of five.

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Tay-Sachs Disease
Tt
Tt
tt
TT or Tt
Tt or TT
Tt or TT
What are the genotypes of all individuals in this
family?
TT or Tt
Tt
Tt
tt
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Cystic Fibrosis

• Found in Caucasians.
• Most common lethal genetic disorder among white
  Americans.
• Autosomal recessive on chromosome 7

• Thick mucus produced in lungs, intestines, and
  pancreas.

• 1/20 of Caucasian population are carriers.
• One in 2,000 children born to white Americans
  inherits the disorder.
• CF kills 500 children and young adults each year.

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Sickle Cell Anemia

• Found in both African Americans and Hispanics of
  Carribbean ancestry (1 in 500 African Americans)

• Hemoglobin (oxygen-carrying protein) differs by
  ONE amino acid.

• Sickling of cells occurs, clogging vessels --
  stroke.

• In U.S., 60,000 people have it 30 million
  carriers.

• Autosomal recessive on chromosome 11

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X-Linked Disorders

• Found on the 23rd pair of chromosomes, i.e., the
  sex chromosomes.

• Usually shows up in males due to Y chromosome
  lacking genes, i.e., one recessive gene in males
  produces disorder.

• Mother carriers pass gene to sons.

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Hemophilia -- Bleeders Disease

• Deficient blood coagulation due to absence of
  coagulation factor 8 that helps cause blood to
  clot.

• 50 of daughters will also be carriers.

• 1 in 7,000 born with it
• X-linked recessive on chromosome X

XHXh
XHY
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Duchennes Muscular Dystrophy

• Progressive destruction of muscles.

• Patients wheelchair bound by teens.

• Female carriers can be detected by presence of
  creatine kinase.

• Can be detected by the 20th week of gestation.

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Duchennes Muscular Dystrophy
XDXd
XDY
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Color Blindness
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Red-Green Color Blindness
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Multiple Alleles

• Blood type, using I gene.
• Human blood types include
• Phenotype Genotype
• A IAIA or IAi
• B IBIB or IBi
• AB IAIB (Universal Recipient)
• O ii (Universal Donor)

If a child has type O blood and its mother has
type A, could a type B man be the father? Why
couldnt a blood test be used to prove he is the
father?