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Chapter 18
Genes and Medical Genetics
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Outline
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Genotype vs. Phenotype
Dominant vs. Recessive Traits
Punnett Squares
Autosomal Recessive Disorders
Autosomal Dominant Disorders
Pedigree Charts
Multiple Allelic Traits
Incomplete Dominance
Sex-Linked Traits
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Organization of human DNA
• 46 individual strands called chromosomes
• almost every cell contains 46 chromosomes stored in the
nucleus - all the information to clone yourself
• 46 chromosomes arranged as 23 pairs: each has a partner
strand inherited from the mother and father. Half of you
is your mom, the other half is your dad.
• all genes on each paired set encode comparable products
except for the sex chromosome pair: XX (female) and
XY (male).
• each member of the pair can encode different versions of the
same gene called alleles
• alleles arise from an original gene through evolutionary
mutation
This sexual reproduction stuff is complex
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Shuffling the genetic deck: making gametes
• for growth and repair, cells need to multiply
• mitosis makes progeny cells with full DNA complement
• full DNA content (2n) is diploid
• for production of reproductive cells, gametes are formed
• gametes: eggs or sperm contain half the original DNA of parent
• meiosis: cell division process leading to gemete formation
• half DNA content (n) is haploid
• only one member of each chromosome pair is used to make
the haploid gametes
• recombination occurs during meiosis to shuffle the alleles
between members of each chromosome pair
• recombination allows mixture of alleles from father and mother
to be passed on in gametes and increases genetic
variability
This sexual reproduction stuff is complex …
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Variability : the result of sexual reproduction
• haploid gametes combine at conception to restore the diploid
chromosome content
• all mitochondrial DNA is inherited from the mother, not father
• alleles are mixed in meiosis, so each combination in the new
individual will be unique
• combinations of genes determines everything from
appearance, physical strengths and weaknesses, even
behavior, intellegence,
intellegence, emotional state
• sexual reproduction creates variety, a opposed to asexual
reproduction occurring through cloning of DNA information
…but Dr. Sussman makes this seem easy
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Genetics: understanding how genes combine to
create the characteristics of an organism
• organisms inherit characteristics discretely through genes
• Charles Darwin thought inheritance was a matter of blending
phenotypic characteristics (didn’
(didn’t know about genes)
• blending would be bad news for natural selection, since any
advantageous evolutionary trait would be diluted out
through subsequent generations
• Gregor Mendel sorted it out and invented the science of
genetics by studying inheritance in the 1930s.
• combination of “natural selection”
selection” and Medelian genetics is
referred to as “new synthesis”
synthesis”
• Mendel had no idea of DNA, but observed specific phenotypes
were passed on in his pea plants in a lawful manner
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Genetics: it works like this…
this…
• alleles are often not equally weighted with regard to producing
a given phenotype
• there are dominant and recessive alleles (e.g. tall versus short)
• if tall is dominant (T) over short (t), the phenotype of an
individual with TT will be tall (both dominant alleles)
• the phenotype of an individual with tt will be short (both
recessive alleles
• both TT or tt are called homozygous - alleles are the same
• the phenotype of an individual with Tt will be tall because the
dominant gene determines the phenotype
• mixed alleles like this are heterozygous
• in real life, genetics are usually more complicated because
many different genes combine together, alleles are not
dominant over each other, influenced by gender,
influenced by environment, or several alleles in the gene
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pool collectively form a hierarchy of dominance
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Genotype and Phenotype
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Genotype refers to an individual’s genes.
– Alleles are alternate forms of a gene.
v Dominant alleles are assigned
uppercase letters, while recessive
alleles are assigned lowercase letters.
ÿ Homozygous Dominant = EE.
ÿ Homozygous Recessive = ee.
ÿ Heterozygous = Ee.
Phenotype refers to an individual’s physical
appearance.
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Genotype determines phenotype
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Dominant/Recessive Traits
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Forming the Genes.
– Reduction of chromosome number
occurs when pairs of chromosomes
separate as meiosis occurs.
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Gametogenesis - splitting up the genes
Gametes have only one allele for each trait
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Figuring the Odds
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A Punnett square is used to determine the
phenotypic ratio among the offspring when
all possible sperm are given an equal
chance to fertilize all possible eggs.
– If both parents are heterozygous, each
child has a 25% chance of exhibiting the
recessive phenotype.
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Inherited characteristics - a few examples
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Heterozygous by heterozygous cross
Punnett square - used to determine phenotypic ratio
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Hetero by homozygous recessive cross
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Dihybrid cross
• children of original pairing
are heterozygous for two
traits
• A 4x4 array yields 16
assortment possibilities in a
ration of 9:3:3:1
• Imagine the possible
variations in the actual
human population - limitless
combinations
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Autosomal Dominant Disorders
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Dominant disorders are passed on by a
parent who has, or will develop, the
disorder.
– Neurofibromatosis.
v Allele located on chromosome 17.
– Huntington Disease.
v Allele located on chromosome 4.
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Autosomal Recessive Disorders
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Recessive disorders can by passed on by
parents who are unaffected.
– Tay-Sachs Disease.
v Allele located on chromosome 15.
– Cystic Fibrosis.
v Allele located on chromosome 7.
– Phenylketonuria.
v Allele located on chromosome 12.
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Autosomal recessive disorders cause disease
• Cystic fibrosis - channel protein
mutation leads to altered Cl
ion transport
• Phenylketonuria - lack enzyme to
metabolize phenylalanine
• Tay-Sachs - lack of enzyme
hexosaminidase A leads to
abnormal storage of
glycosphingolipid in lysosomes
• Albanism - mutation of pigment
gene melanin leading to lack
of coloration
Epistasis:
Epistasis: one gene affects expression of
others (e.g. albinos also exhibit loss of
pigment, so any genes responsible for
coloration are not expressed
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Twin traits: concordance suggests hereditary
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Beyond Simple Inheritance
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Polygenic Inheritance.
– One trait is governed by two or more sets
of alleles.
v Continuous variation of phenotypes.
ÿ Skin Color.
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Polygenic inheritance - multiple alleles
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Beyond Simple Inheritance
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Multiple Allelic Traits.
– Gene exists in several allelic forms,
although an individual usually only has
two of the possible alleles.
v ABO Blood Types.
ÿ A - A antigen on red blood cells.
ÿ B - B antigen on red blood cells.
ÿ O - Neither A or B antigen on red
blood cells.
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Inheritance of blood type: multiple alleles
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Beyond Simple Inheritance
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Incomplete Dominance.
– Codominance occurs when alleles are
equally expressed in a heterozygote.
– Incomplete Dominance is exhibited when
the heterozygote has an intermediate
phenotype between that of either
heterozygote.
v Sickle Cell Disease.
ÿ Heterozygotes protected from malaria.
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Incomplete dominance: intermediate phenotype
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Sex-Linked Traits
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Traits controlled by alleles on the sex
chromosomes are said to be sex-linked.
– X chromosome = X-linked.
– Y chromosome = Y-linked.
Most sex-linked alleles are on the X
chromosome.
– Red-Green Color Blindness.
– Muscular Dystrophy.
– Hemophilia.
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Barr bodies: inactivated X chromosome
• keeps sex-linked dosage constant
• recessive mutations appear in females as mosaics
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Sex linked trait - color blindness
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Color blind females are more rare than males - need 2 recessive alleles
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X-linked disorders cause disease
• Color blindness:
blindness: lacking
appropriate pigment
in cone cells of retina
• Muscular dystrophy:
dystrophy:
abnormal dystrophin
gene
• Hemophilia:
Hemophilia: lack clotting
factor VIII (A-type)
or IX (B-type)
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Sex-influenced traits - hormonal effects
Testosterone
causes effect
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Review
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Genotype vs. Phenotype
Dominant vs. Recessive Traits
Punnett Squares
Autosomal Recessive Disorders
Autosomal Dominant Disorders
Pedigree Charts
Multiple Allelic Traits
Incomplete Dominance
Sex-Linked Traits
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Remember:
• a given mutation in a gene that produces a beneficial
consequence for the organisms capacity to reproduce can
be spread as a distinct advantage to subsequent
generations and will not be diltued out
• genes are inherited as distinct entities
This sexual reproduction stuff is complex,
but Dr. Sussman makes it seem easy
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