Mendelian pedigree, HardyWeinberg eqn

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Lecture 4 Mendelian pedigree,
Hardy-Weinberg eqn Explanation of the following
terms Mendelian character -The presence or
absence of the simplest genetic character depends
on the presence of a genotype at a single
locus. In humans - 10,000 mendelian characters
known. Characters can be disease-causing/patholog
ical or non- Pathological. See OMIM
database Dominant and recessive Are properties
of characters not a gene Character is dominant
when it manifests in the heterozygote Character
is recessive when it manifests only in the
homozygote Phenotype The observable
characteristics of a cell or organism Genotype Th
e genetic constitution of an individual at a
specific locus
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Main symbols used in pedigrees

• generations are usually labeled in roman
• numerals and individuals in arabic numeral
• Example - III 7/III7

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5 Basic mendelian pedigree patterns
A. Autosomal dominant

• affected parent has at least on affected parent
• affects either sex
• transmitted by either sex
• child of an unaffected x unaffected mating
• has 50 chance of being affected

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Autosomal recessive

• affected people are usually born to affected
  parents
• parents of affected people are usually
  asymptomatic
• carriers
• increased incidence of parental consaguinity
• affects either sex
• after birth of an affected child, each
  subsequent child
• has a 25 chance of being affected

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X-linked recessive inheritance

• affects mainly males
• affected males are born to unaffected parents
• mother is normally an asymptomatic carrier
• and may have affected male relatives
• females may be affected if the father is
  affected
• and mother is a carrier
• there is no male-to-male transmission in the
• pedigree

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Haemophilia - X-linked recessive inheritance A
severe disorder of blood clotting recessive
allele is involved. Affected lack clotting factor
VIII. Suffer From excessive bleeding after injury
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• Her one son, Leopold was hemophilic,
• her 2 daughters were carriers
• two granddaughters were carriers by marriage
• introduced the gene into royal families of
  Russia
• And Spain
• the present royal family is descended from a
  normal
• son of Victoria and is free of the disease

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X-linked dominant inheritance

• affects either sex
• females are often more mildly affected
• the child of an affected female, regardless of
  its
• sex, has a 50 chance of being affected
• for an affected male, all his daughters, but
  none
• of his sons are affected

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Y-linked inheritance

• affects only males
• affected males always have an affected father
• all sons of an affected man are affected

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Mitochondrial inheritance
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• mitochondrial mutations causes a significant
• number of human genetic disease
• have 2 unusual features
• Matrilineal inheritance because sperm do not
• contribute to mitochondria of the zygote. The
• mitochondria can affect both sexes, but is passed
• on only by affected mothers
• Frequent heteroplasmy- when mixture
• of normal and mutant mitochondrial
• genomes are seen within each cell. Additionally
• Mitochondrial heteroplasmy can be transmitted
• From heteroplasmic mother to heteroplasmic child
• Lebers disease MIM 535000 causes sudden and
• irreversible loss of sight

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Complications to basic pedigree patterns
Various complications disguise the basic
mendelian patterns. Exercise Explain the
following terms (i) Penetrance (ii)
Anticipation (iii) Mosaicism (iv) Chimeras
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Hardy-Weinberg distribution
Is the simple relationship between gene
frequencies and genotype frequencies that is
found in a population under certain conditions.
Hardy-Weinberg distribution is used in
genetic counselling to calculate carrier
frequencies and genetic risks
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Nonmendelian characters

• 2 schools of thought
• A. Mendelian inheritance- requires dichotomous
• characters eg extra fingers (have or dont
  have)
• B. Polygenic inheritance- continuous or
  quantitative
• characters
• Cannot use mendelian analysis such
• as body size, build and strength (Galton,
  Fischer)
• Multifactorial diseases such as schizophrenia
  
• Dependent on 2/3 or many genetic loci,
  possible
• contribution from environmental factors
• For dichotomous characters susceptibility
  genes
• For quantitative characters quantitative
• trait loci or QTLA