Pedigree analysis
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Transcript of Pedigree analysis
Pedigree Analysis
Classical Genetics
• Mendelian inheritance describes inheritance patterns that obey two laws– Law of segregation – Law of independent assortment
• Simple Mendelian inheritance involves – A single gene with two different alleles– Alleles display a simple dominant/recessive
relationship
Wild-type (dominant) allele Mutant (recessive) allelePurple flowers White flowers
Axial flowers Terminal flowers
Yellow seeds Green seeds
Round seeds Wrinkled seeds
Smooth pods Constricted pods
Green pods Yellow pods
Tall plants plants
• Consider, for example, the traits that Mendel studied
• Another example is from Drosophila
Wild-type (dominant) allele Mutant (recessive) alleleRed eyes White eyes
Normal wings Miniature wings
• Human genetic diseases caused by recessive mutant alleles– The mutant alleles do not produce fully
functional proteins
Lethal Alleles• Essential genes are those that are
absolutely required for survival– The absence of their protein product leads to a
lethal phenotype• It is estimated that about 1/3 of all genes are
essential for survival
• Nonessential genes are those not absolutely required for survival
• A lethal allele is one that has the potential to cause the death of an organism – These alleles are typically the result of
mutations in essential genes– usually recessive, but can be dominant
• Many lethal alleles prevent cell division
• Some lethal allele exert their effect later in life– Huntington disease
• Characterized by progressive degeneration of the nervous system, dementia and early death
• The age of onset of the disease is usually between 30 to 50
• Conditional lethal alleles may kill an organism only when certain environmental conditions prevail – Temperature-sensitive (ts) lethals
• A developing Drosophila larva may be killed at 30 C• But it will survive if grown at 22 C
Lethal Alleles
• Every gene carries information telling the body how to make a particular protein. – Adult cells have two copies of each gene. – If one copy of the gene doesn’t work, the cell
has a backup.
• New versions of genes can be produced by mutations– These new alleles can produce proteins that
either• Do not work• Or do something they’re not supposed to
• Thus any condition associated with this is referred to as a genetic disease
• Cystic fibrosis (CF)– A recessive disorder of humans– About 3% of caucasians are carriers – The gene encodes a protein called the cystic
fibrosis transmembrane conductance regulator (CFTR)• The CFTR protein regulates ion transport across
cell membranes
– The mutant allele creates an altered CFTR protein that ultimately causes ion imbalance• This leads to abnormalities in the pancreas, skin,
intestine, sweat glands and lungs
Example: Cystic fibrosisThe cell membranes of the cells lining the lungs and air passages contain CF membrane proteins
Cell membrane CF membrane proteins
The CF protein pumps chloride ions from one side of the membrane to the other
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The CF protein produces a higher concentration of chloride ions on one side of the membrane than the other
…osmosis.
H2OH2O
H2O
Cell membrane
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Water molecules follow the chloride ions across the semi-permeable cell membranes by…
H2OH2O
H2O
The body uses the CF chloride pump to move water into secretions like the mucus found in the trachea and sweat.
If your cells cannot make working chloride pumps, your mucus becomes too thick and sticky due to lack of water
However, to make a functioning chloride pump, each cell only needs one good copy of the gene for it.
So, cystic fibrosis is recessive
Cc
Defective gene produces non-working chloride pump
Healthy gene produces working chloride pump
This individual does not suffer from cystic fibrosis,but is a carrier
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c c
This individual will suffer from cystic fibrosis
REMEMBER: Genes do NOT exist to cause disease…
… defective genes cause disease
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Neither copy of the gene carried by this individual can produce a working chloride pump
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Pedigree Analysis
• In the study of human traits, there are not controlled parental crosses
• Rely on information from family trees or pedigrees
• Pedigree analysis is used to determine the pattern of inheritance of traits in humans
Figure 2.10
Pedigree Symbols
Pedigree Analysis
• Pedigree analysis is commonly used to determine the inheritance pattern of human genetic diseases
• Genes that play a role in disease may exist as– A normal allele – A mutant allele that causes disease symptoms
• Disease that follow a simple Mendelian pattern of inheritance can be– Dominant – Recessive
• A recessive pattern of inheritance makes two important predictions– 1. Two normal heterozygous individuals will
have, on average, 25% of their offspring affected
– 2. Two affected individuals will produce 100% affected offspring
• A dominant pattern of inheritance predicts that– An affected individual will have inherited the
gene from at least one affected parent– Alternatively, the disease may have been
the result of a new mutation that occurred during gamete formation
Figure 2.10