Autosomal Dominant Autosomal Dominant InheritanceInheritance Autosomal Autosomal

dominant dominant inheritance occurs inheritance occurs when one copy of when one copy of an allele is an allele is sufficient for sufficient for expression of a expression of a trait and the gene trait and the gene is located on one of is located on one of the 22 autosomes.the 22 autosomes.

Chapter 7: Human Chapter 7: Human GeneticsGenetics

Each affected person has at least one affected parent. An affected person has a 50% chance of passing the trait to a child.Males and females are equally likely to be affected. Two affected people can have an unaffected child.

Autosomal Dominant Autosomal Dominant DisordersDisorders Progeria:Progeria: characterized by an characterized by an

appearance of accelerated aging in appearance of accelerated aging in children, affects 1 in 8 million newbornschildren, affects 1 in 8 million newborns

Huntington’s DiseaseHuntington’s Disease: degenerative : degenerative brain disorder, slowly diminishes the brain disorder, slowly diminishes the affected individual’s ability to walk, affected individual’s ability to walk, think, talk and reason think, talk and reason dementia dementia

Autosomal Recessive Autosomal Recessive InheritanceInheritance

Autosomal recessive Autosomal recessive inheritance occurs inheritance occurs when two copies of an when two copies of an altered gene located on altered gene located on one of the autosomes one of the autosomes must be present for an must be present for an individual to be individual to be affected with the trait affected with the trait or condition or condition determined by that determined by that gene.gene.

An affected individual (homozygote) has two parents who are unaffected but An affected individual (homozygote) has two parents who are unaffected but each parent carries the altered gene (heterozygote).each parent carries the altered gene (heterozygote).

Males and females are at equal risk for being affected.Males and females are at equal risk for being affected. Two affected individuals usually produce children all of whom are affected as Two affected individuals usually produce children all of whom are affected as

well.well.

Autosomal Recessive Autosomal Recessive DisordersDisorders

Tay-Sachs DiseaseTay-Sachs Disease: individuals lack an : individuals lack an enzyme in the lysosomes of their brain cells enzyme in the lysosomes of their brain cells needed to break down lipids. The undigested needed to break down lipids. The undigested lipids enlarge and eventually destroy the lipids enlarge and eventually destroy the brain cells that house them.brain cells that house them.

Phenylketonuria (PKU):Phenylketonuria (PKU): individuals lack an individuals lack an enzyme that converts Phe to Tyr. Failure of enzyme that converts Phe to Tyr. Failure of the conversion to take place results in a the conversion to take place results in a buildup of Phe. Through a mechanism that is buildup of Phe. Through a mechanism that is not well understood, the excess Phe is toxic to not well understood, the excess Phe is toxic to the central nervous system. This results in the central nervous system. This results in mental retardation and other neurological mental retardation and other neurological problems if not detected early.problems if not detected early.

AlbinismAlbinism

X-Linked InheritanceX-Linked Inheritance Most individuals who are affected with the trait or Most individuals who are affected with the trait or

condition in questions are males.condition in questions are males. Mothers of the affected males are carriers and the Mothers of the affected males are carriers and the

sisters of affected males may be either carriers or sisters of affected males may be either carriers or not carry the gene al all. The basis for X-linked not carry the gene al all. The basis for X-linked inheritance is that females have two X chromosomes inheritance is that females have two X chromosomes and males have only one X chromosome.and males have only one X chromosome.

Affected males are hemizygous (their one X Affected males are hemizygous (their one X chromosome has the mutant allele)chromosome has the mutant allele)

Affected females are homozygous (both X Affected females are homozygous (both X chromosomes have the mutant allele)chromosomes have the mutant allele)

Affected males transmit the gene to all daughters, but Affected males transmit the gene to all daughters, but not to any of their sonsnot to any of their sons

The daughters of an affected male will usually be a The daughters of an affected male will usually be a carrier (heterozygote) and thus not show the trait carrier (heterozygote) and thus not show the trait (masked)(masked)

Sons of heterozygous females have a 50% chance of Sons of heterozygous females have a 50% chance of receiving the gene and thus expressing the trait or receiving the gene and thus expressing the trait or conditioncondition

X-linked X-linked DisordersDisorders Colour BlindnessColour Blindness

In red-green colour vision deficiency, the In red-green colour vision deficiency, the

visible spectrum is divided into two parts; visible spectrum is divided into two parts;

a red segment and a blue segment, separateda red segment and a blue segment, separated

by grey or indistinct areas. The amount of greyby grey or indistinct areas. The amount of grey

or indistinct areas varies according to the or indistinct areas varies according to the severity of the deficiency.severity of the deficiency.

Men are mainly affectedMen are mainly affected For a woman to be colour deficient, her father For a woman to be colour deficient, her father

must be colour-blind and her mother must be a must be colour-blind and her mother must be a carriercarrier

A defective male always inherits his deficiency A defective male always inherits his deficiency from his mother who usually has normal colour from his mother who usually has normal colour vision is therefore a carrier of the defect.vision is therefore a carrier of the defect.

Duchenne Muscular DystrophyDuchenne Muscular Dystrophy Involves the wasting away of muscle Involves the wasting away of muscle

tissuetissue Muscle cells become engorged with fat Muscle cells become engorged with fat

and they eventually waste away most and they eventually waste away most individuals suffer from respiratory individuals suffer from respiratory failure in their early twenties.failure in their early twenties.

Human Pedigrees: Working out Human Pedigrees: Working out Inheritance PatternsInheritance Patterns Pedigrees are a convention for keeping track of Pedigrees are a convention for keeping track of

human genetic traits used to infer genotype. human genetic traits used to infer genotype. Pedigrees are the human equivalent of test Pedigrees are the human equivalent of test

crosses. crosses. In a visualization of a pedigree: In a visualization of a pedigree: males are designated with square symbols. males are designated with square symbols. females with round symbols females with round symbols lines are drawn to indicated matings, parent-lines are drawn to indicated matings, parent-

offspring relationships, and relationships between offspring relationships, and relationships between siblings. siblings.

Factors to Consider in PedigreesFactors to Consider in PedigreesIs the trait located on a sex chromosome or an Is the trait located on a sex chromosome or an autosome?autosome?

Autosomal – not on a sex chromosomeAutosomal – not on a sex chromosomeSex Linkage – located on one of the sex Sex Linkage – located on one of the sex chromosomeschromosomes

Y-linked - only males carry the trait.Y-linked - only males carry the trait.X-linked (recessive) - sons inherit the disease X-linked (recessive) - sons inherit the disease from normal parentsfrom normal parents

How is the trait expressed?How is the trait expressed?Dominant - the trait is expressed in every Dominant - the trait is expressed in every generation.generation.Recessive - expression of the trait may skip Recessive - expression of the trait may skip generations.generations.

Pedigree Pedigree Diagrams: Diagrams:

II Basic SymbolsBasic Symbols

Pedigree Pedigree Diagrams: Diagrams:

IIIIBasic Symbols for offspring and the expression of a trait.

The offspring are depicted below the parents.Filling the symbol with black indicates the expression of the studied trait.

Note that the symbols for non-identical Note that the symbols for non-identical twins and for identical twins differ by twins and for identical twins differ by whether they descend from a common whether they descend from a common

vertical before bifurcatingvertical before bifurcating

PedigreesPedigrees Generations are Generations are

numbered from the top numbered from the top of the pedigree in of the pedigree in uppercase Roman uppercase Roman numerals, I, II, III etc. numerals, I, II, III etc. Individuals in each Individuals in each generation are generation are numbered from the left numbered from the left in arab numberals as in arab numberals as subscripts, III1 , III2, III3 subscripts, III1 , III2, III3 etc. For example, here is etc. For example, here is a typical autosomal a typical autosomal dominant pedigree with dominant pedigree with numbered generations numbered generations and individuals.and individuals.

Marfan’s Syndrome: An Marfan’s Syndrome: An ExampleExample

Expressed in both sexes.Expressed in both sexes. Thus, autosomal.Thus, autosomal.

Expressed in every Expressed in every generation.generation. Thus, dominant.Thus, dominant.

Marfan’s: Genotype the Marfan’s: Genotype the Normal IndividualsNormal Individuals

Assign codes for the alleles.Assign codes for the alleles. Code “m” for the recessive normal Code “m” for the recessive normal

allele.allele. Code “M” for the dominant allele for Code “M” for the dominant allele for

Marfan’s syndrome.Marfan’s syndrome.

Normal individuals must be Normal individuals must be “mm.”“mm.”

Marfan’s: Genotype the Marfan’s: Genotype the Affected IndividualsAffected Individuals

Affected individuals must have Affected individuals must have at least one “M.”at least one “M.”

Marfan’s: Parent-Offspring Marfan’s: Parent-Offspring RelationshipsRelationships

Possibilities for #1 and #2: Heterozygote Possibilities for #1 and #2: Heterozygote (Mm) or homozygous for “M?”(Mm) or homozygous for “M?”

If “MM,” all offspring from a normal mate If “MM,” all offspring from a normal mate should be affected.should be affected.

Therefore, both must be heterozygotes.Therefore, both must be heterozygotes.

Marfan’s: Parental Marfan’s: Parental Genotypes KnownGenotypes Known

““M” must have come from the M” must have come from the mother.mother.

The father can contribute only The father can contribute only “m.”“m.”

Thus, the remaining genotypes Thus, the remaining genotypes are “Mm.”are “Mm.”

Albinism: An ExampleAlbinism: An Example Expressed in both sexes Expressed in both sexes

at approximately equal at approximately equal frequency.frequency. Thus, autosomal.Thus, autosomal.

Not expressed in every Not expressed in every generation.generation. Thus, recessive.Thus, recessive.

Albinism: Genotype the Albinism: Genotype the Affected IndividualsAffected Individuals

Assign codes for the alleles.Assign codes for the alleles. Code “A” for the dominant normal allele.Code “A” for the dominant normal allele. Code “a” for the recessive allele for albinism.Code “a” for the recessive allele for albinism.

Affected individuals must be homozygous for “a.”Affected individuals must be homozygous for “a.” First generation parents must be “Aa” because First generation parents must be “Aa” because

they have normal phenotypes, but affected they have normal phenotypes, but affected offspring.offspring.

Albinism: Genotype the Albinism: Genotype the Normal IndividualsNormal Individuals

Normal individuals must have at Normal individuals must have at least one “A.”least one “A.”

Albinism: Parent-Offspring Albinism: Parent-Offspring RelationshipsRelationships

#1 must transmit “a” to each offspring.#1 must transmit “a” to each offspring. The “A” in the offspring must come from the The “A” in the offspring must come from the

father.father. Normal father could be either heterozygous Normal father could be either heterozygous

or homozygous for an “A.”or homozygous for an “A.”

Albinism: Parental Genotypes are Albinism: Parental Genotypes are KnownKnown

Both parents are heterozygous.Both parents are heterozygous. Normal offspring could have Normal offspring could have

received an “A” from either received an “A” from either parent, or from both.parent, or from both.

Albinism: One Parental Genotype Albinism: One Parental Genotype is Knownis Known

Only the genotype of the Only the genotype of the offspring expressing albinism offspring expressing albinism are known.are known.

Normal offspring must have Normal offspring must have received an “a” from their received an “a” from their affected father.affected father.

Hairy Ears: An ExampleHairy Ears: An Example Only males are affected.Only males are affected. All sons of an affected father All sons of an affected father

have hairy ears. have hairy ears. Thus, hairy ears is Y-linked.Thus, hairy ears is Y-linked.

Hairy Ears: Female Sex Hairy Ears: Female Sex DeterminationDetermination

All females are XXAll females are XX

Hairy Ears: Male Sex Hairy Ears: Male Sex DeterminationDetermination

All males are XY.All males are XY.

Hairy Ears: Gene on the Y Hairy Ears: Gene on the Y ChromosomeChromosome

Code “H” indicates the allele on Code “H” indicates the allele on the Y chromosome for hairy earsthe Y chromosome for hairy ears

Hairy Ears: Wild-Type Allele Hairy Ears: Wild-Type Allele for Normal Earsfor Normal Ears

Code “+” indicates the allele on Code “+” indicates the allele on the Y chromosome for normal the Y chromosome for normal ears.ears.

Hemophilia: An ExampleHemophilia: An Example In this pedigree, only males are affected, and In this pedigree, only males are affected, and

sons do not share the phenotypes of their sons do not share the phenotypes of their fathers.fathers. Thus, hemophilia is linked to a sex chromosome–the X.Thus, hemophilia is linked to a sex chromosome–the X.

Expression of hemophilia skips generations.Expression of hemophilia skips generations. Thus, it is recessive.Thus, it is recessive.

Extensive bruising of the

left forearm and hand in a patient with hemophilia.

Hemophilia: Hemophilia: Expression of the Female Sex Expression of the Female Sex

ChromosomesChromosomes All females are XXAll females are XX

Hemophilia: Hemophilia: Expression of Male Sex Expression of Male Sex

ChromosomesChromosomes All males are XY.All males are XY.

Hemophilia: Genotype the Affected Hemophilia: Genotype the Affected IndividualsIndividuals

Assign codes for the alleles.Assign codes for the alleles. Code “H” for the recessive hemophilia allele.Code “H” for the recessive hemophilia allele. Code “+” for the wild-type normal allele.Code “+” for the wild-type normal allele.

Affected individuals must have an “H” on an X Affected individuals must have an “H” on an X chromosome.chromosome.

Hemophilia: Father-Hemophilia: Father-Daughter RelationshipDaughter Relationship

All daughters of an affected All daughters of an affected father receive an X chromosome father receive an X chromosome with the “H” allele.with the “H” allele.

Hemophilia: Genotyping the Hemophilia: Genotyping the Normal IndividualsNormal Individuals

Normal individuals must have at Normal individuals must have at least one X chromosome with least one X chromosome with the wild-type allele, “+.”the wild-type allele, “+.”

Hemophilia: Homozygous Hemophilia: Homozygous or Heterozygous?or Heterozygous?

Only males affectedOnly males affected Not Y-linkedNot Y-linked Skips a generation: recessiveSkips a generation: recessive X-linkedX-linked

Try It!Try It!

Let us begin by drawing the Let us begin by drawing the pedigree described below (which is pedigree described below (which is not necessarily an autosomal not necessarily an autosomal dominant condition and which dominant condition and which contains extraneous information).contains extraneous information).

The ScenarioThe Scenario Alice and Bob have a two year old son, Charles, Alice and Bob have a two year old son, Charles,

who is showing mental retardation, short stature, who is showing mental retardation, short stature, micropenis, and cryptorchidism. Alice has two micropenis, and cryptorchidism. Alice has two living, unaffected, brothers but her eldest living, unaffected, brothers but her eldest brother died at age 9 and a second brother died brother died at age 9 and a second brother died aged 10 months. Both had similar problems to aged 10 months. Both had similar problems to Charles. Alice's father, David, who was Charles. Alice's father, David, who was symptomless, has a sister, Ethel, who has an symptomless, has a sister, Ethel, who has an unaffected boy and girl, and a brother, Fred, who unaffected boy and girl, and a brother, Fred, who also has two unaffected children. Alice's mother, also has two unaffected children. Alice's mother, Gertrude, has two living sisters and had a Gertrude, has two living sisters and had a brother who had died in childhood and who, she brother who had died in childhood and who, she remembers, had been mentally retarded. Bob has remembers, had been mentally retarded. Bob has two brothers, Henry and Ignatius, who are still two brothers, Henry and Ignatius, who are still unmarried. His parents, John and Kate, had unmarried. His parents, John and Kate, had tragic lives, both were adopted and never knew tragic lives, both were adopted and never knew their biological parents and both died as the their biological parents and both died as the result of a road accident.result of a road accident.

Step 1 Step 1

Begin with Alice, Begin with Alice, Bob and Charles.Bob and Charles.

Here are three Here are three possible drawings possible drawings of this nuclear of this nuclear family.family.

Correct Solution Correct Solution

Alice and Bob are connected by a Alice and Bob are connected by a horizontal line to show that this is a horizontal line to show that this is a mating. Charles is connected to that mating. Charles is connected to that horizontal line to show that he is a horizontal line to show that he is a product of that mating. product of that mating.

Choose One…Choose One…

Step 2 •Now add Alice's siblings and parents to the pedigree.

Correct Solution was Correct Solution was Possiblilty 3Possiblilty 3

Alice and her four brothers are connected vertically to a horizontal line which is, in turn, connected to the line drawn between her parents David and Gertrude. Her two dead brothers (whom we presume died of the same genetic disease - though this can sometimes be a foolish assumption without medical evidence) are shaded in (to show that they suffered from the disease) and are crossed through (to show that they are dead).

Step 3 Step 3

Now add Gertrude's siblings to the Now add Gertrude's siblings to the pedigree. pedigree.

And David's siblings and his And David's siblings and his nephews and nieces nephews and nieces

Finally add Bob's side of the family Finally add Bob's side of the family Try Drawing it!!!Try Drawing it!!!

Correct Drawing!Correct Drawing!