PEDIGREE ANALYSIS

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PEDIGREE ANALYSIS
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HUMAN PEDIGREE ANALYSIS

http//medicine.creighton.edu/medschool/2002/lectu
res/990113/sld002.htm
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HUMAN PEDIGREE ANALYSIS

http//medicine.creighton.edu/medschool/2002/lectu
res/990113/sld002.htm
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HUMAN PEDIGREE DEFINITIONS

• PROBAND - individual through whom the family
• came to your attention (arrow)
• CONSULTAND - individual seeking your advice
• (C double bar)
• PROSITUS INDEX CASE - same as proband

http//medicine.creighton.edu/medschool/2002/lectu
res/990113/sld002.htm
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MODES OF INHERITANCE

• autosomal dominant
• autosomal recessive
• sex-linked dominant
• sex-linked recessive
• mitochondrial inheritance
• multifactorial inheritance

http//medicine.creighton.edu/medschool/2002/lectu
res/990113/sld002.htm
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DENTINOGENESIS IMPERFECTA

• autosomal dominant mode of inheritance
• frequency may be 1 in 6000 to 8000 children
• involves opalescent dentin that makes teeth
  blue-gray or amber brown
• on dental radiographs, the teeth have bulbous
  crowns, roots that are narrower than normal, and
  pulp chambers and root canals that are smaller
  than normal or completely obliterated

http//wsrv.clas.virginia.edu/rjh9u/dentimp.html
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AUTOSOMAL DOMINANT PEDIGREE EXAMPLE
http//medicine.creighton.edu/medschool/2002/lectu
res/990113/sld002.htm
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ATTRIBUTES AUTOSOMAL DOMINANT

• every affected individual has an affected parent
• 50 chance that each parent will transmit the
  trait to
• any child
• affected numbers of males and females are
  roughly
• equal
• two affected individuals may have unaffected
  children
• in homozygous dominant individuals the phenotype
  
• is often more severe than the heterozygous
  phenotype

http//wsrv.clas.virginia.edu/rjh9u/dentimp.html
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AUTOSOMAL RECESSIVE PEDIGREE EXAMPLE
This example shows the inheritance of albinism in
a family
http//biotype.biology.dal.ca/steve/jwright/3.16.
jpg
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ALBINISM

• autosomal recessive mode of inheritance
• the lack of pigmentation in skin, hair, and
  eyes
• the brown pigment melanin cannot be made by
  albinos
• several mutations may cause albinism
• 1) the lack of one or another enzyme along the
  melanin-producing pathway
• 2) the inability of the enzyme to enter the
  pigment cells and convert the amino acid tyrosine
  into melanin

http//gened.emc.maricopa.edu/bio/bio181/BIOBK/Bio
Bookhumgen.html
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ATTRIBUTES AUTOSOMAL RECESSIVE

• for rare traits most affected individuals are
  the
• children of unaffected parents
• all of the children of two affected (homozygous)
  
• individuals are affected
• the risk of an affected child from a mating of
  two
• heterozygotes is 25
• trait is expressed in both males and females in
• roughly equal numbers
• for rare traits, the unaffected parents of an
  affected
• individual may be related to each other

http//wsrv.clas.virginia.edu/rjh9u/dentimp.html
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SEX-LINKED PEDIGREE EXAMPLE

This example shows the inheritance of
color-blindness in a family
http//wsrv.clas.virginia.edu/rjh9u/xped.html
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COLOR BLINDNESS

• Sex-linked recessive mode of inheritance
• afflicts 8 of males and 0.04 of human females.
• color perception depends on three genes, each
  producing chemicals sensitive to different parts
  of the visible light spectrum - red and green
  detecting genes are on the X-chromosome

http//gened.emc.maricopa.edu/bio/bio181/BIOBK/Bio
Bookhumgen.html
http//www.geocities.com/Heartland/8833/coloreye.h
tml
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EUROPEAN ROYALTY HEMOPHILIA
http//wsrv.clas.virginia.edu/rjh9u/roylhema.html
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HEMOPHILIA

• sex-linked recessive disorder characterized by
  the inability to properly form blood clots
• affects males much more frequently (1 in
  10,000) than females (1 in 100,000,000)
• Until recently, hemophilia was untreatable,
  and only few hemophiliacs survived to
  reproductive age because any small cut or
  internal hemorrhaging after even a minor bruise
  were fatal
• Now treated with blood transfusions and
  infusions of a blood derived substance known as
  anti-hemophilic factor

http//wsrv.clas.virginia.edu/rjh9u/roylhema.html
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OMIM A TOOL FOR SINGLE GENE STUDIES
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A TECHNOLOGICAL TOOL - OMIM

• OMIM - Online Mendelian Inheritance in Man
  database is a catalog of human genes and genetic
  disorders
• authored and edited by Dr. Victor A. McKusick
  and his colleagues at Johns Hopkins
• developed for the World Wide Web by NCBI, the
  National Center for Biotechnology Information
• contains textual information, pictures, and
  reference information
• the OMIM Morbid Map is a catalog of genetic
  diseases and their cytogenetic map locations
  arranged alphabetically by disease

http//www3.ncbi.nlm.nih.gov/Omim/
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A TECHNOLOGICAL TOOL - OMIM

Access OMIM via the following address http//www
3.ncbi.nlm.nih.gov/Omim/
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PKU EXAMPLE after searching for PKU keyword
Select Entries from OMIM -- Online Mendelian
Inheritance in Man 10 entries found, searching
for "pku" 261600 PHENYLKETONURIA 261630
PHENYLKETONURIA II 208400 ASPARTYLGLUCOSAMINURIA
261640 6-_at_PYRUVOYLTETRAHYDROPTERIN SYNTHASE
PTS 234500 HARTNUP DISORDER 252800
MUCOPOLYSACCHARIDOSIS TYPE I 253260 BIOTINIDASE
BTD 143100 HUNTINGTON DISEASE HD 264070
HYPERPHENYLALANINEMIA WITH PRIMAPTERINURIA 600225
GTP CYCLOHYDROLASE I GCH1
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PKU EXAMPLE under top entry

• 261600 PHENYLKETONURIA
• Alternative titles symbols
• PKUPHENYLALANINE HYDROXYLASE DEFICIENCYPAH
  DEFICIENCYOLIGOPHRENIA PHENYLPYRUVICAFOLLING
  DISEASEPHENYLALANINE HYDROXYLASE, INCLUDED PAH,
  INCLUDEDPKU1, INCLUDEDHYPERPHENYLALANINEMIA,
  MILD, INCLUDED HPA, INCLUDEDPHENYLALANINEMIA,
  INCLUDED

http//www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispm
im?261600
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PKU EXAMPLE overall organization

• EVOLUTION
• ANIMAL MODEL
• HISTORY
• ALLELIC VARIANTS
• View List of allelic variants
• REFERENCES
• SEE ALSO
• CONTRIBUTORS
• CREATION DATE
• EDIT HISTORY
• MINI-MIM
• CLINICAL SYNOPSIS

• TABLE OF CONTENTS
• DESCRIPTION
• CLINICAL FEATURES
• BIOCHEMICAL FEATURES
• INHERITANCE
• MAPPING
• MOLECULAR GENETICS
• DIAGNOSIS
• CLINICAL MANAGEMENT
• POPULATION GENETICS
• EVOLUTION

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MITOCHONDRIAL INHERITANCE
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MATERNAL INHERITANCE

• during zygote formation sperm contribute only
  the paternal nuclear genome
• in addition to the materal genome, all
  cytoplasmic components including mitochondria are
  contributed by the egg
• mitochondrial DNA of a zygote is therefore
  determined exclusively by the mother and is
  passed intact through maternal lines of
  inheritance

http//www.umdf.org/INFO.HTMMitochondriaAndDiseas
e
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MITOCHONDRIAL DNA

• constitutes around 1 of cellular DNA
• each mitochondrion carries 2-10 copies of
  mitochondrial (mt) DNA
• mitochondrial genetic code is similar to the
  nuclear code, but mtDNA has several
  distinguishing features related to its small 16kb
  size
• the mitochondrial genome is very compact
• adjacent genes overlap
• no introns (non-coding segments of DNA)

http//www.umdf.org/frame/INFO_F.HTM
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MITOCHONDRIAL DNA
http//cellbio.utmb.edu/cellbio/mitoch2.htm
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MITOCHONDRIAL DISEASE

• when mutations occur in mitochondrial DNA which
  affect the mitochondrias function, the vital
  supply of ATP to organ systems can be disrupted
• cells that require the most energy, like the
  brain, heart and skeletal muscles, are most
  vulnerable

http//cellbio.utmb.edu/cellbio/mitoch2.htm
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MITOCHONDRIAL DISEASE

• Individuals with a mitochondrial disease can
  exhibit a vast array of symptoms that include

• respiratory disorders
• diabetes
• liver disease
• susceptibility to infection
• developmental delays, learning disabilities or
  retardation
• neurological problems and seizures

poor growth loss of motor control muscle
weakness visual and/or hearing problems cardiac
disease gastric-intestinal disorders
http//www.umdf.org/INFO.HTMMitochondriaAndDiseas
e
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MITOCHONDRIAL DISEASE

• the genetics involved in mitochondrial
  disorders are complex because the mitochondrias
  function is determined by both its own
  mitochondrial DNA (maternal inheritance) and the
  cell's nuclear DNA (autosomal and sex-linked
  inheritance
• in spite of this complexity, since 1988 more
  than 30 point mutations on the mitochondrial
  genome have been located

http//www.umdf.org/INFO.HTMMitochondriaAndDiseas
e