Inheritance of Gene Differences – Inheritance of Gene Differences – non-Mendelian geneic interactions, part 2non-Mendelian geneic interactions, part 2

II.II. Autosomes v. Sex chromosomesAutosomes v. Sex chromosomesA.A. Morgan’s experimentsMorgan’s experiments

B.B. Pattern of Sex linked inheritancePattern of Sex linked inheritance

III.III. Human Genetics & PedigreesHuman Genetics & Pedigrees

II. Sex chromosomes v. II. Sex chromosomes v. AutosomesAutosomes

Sex chromosomes: house some key genes Sex chromosomes: house some key genes responsible for determination of separate sexesresponsible for determination of separate sexes

A.A. Heterogametic, XY or ZWHeterogametic, XY or ZW X & Y differ in size, but they do share a region of X & Y differ in size, but they do share a region of

homology for proper pairing during cell divisionhomology for proper pairing during cell division Genes located on the differential part of the X are Genes located on the differential part of the X are

called X linked genescalled X linked genes

B.B. Homogametic, XX or ZZHomogametic, XX or ZZX & Y differ in size, but they do share a region of homology X & Y differ in size, but they do share a region of homology for proper pairing during cell divisionfor proper pairing during cell divisionGenes located on the differential part of the X are called X Genes located on the differential part of the X are called X linked geneslinked genes

C.C. Autosomes = the remaining (non-sex) Autosomes = the remaining (non-sex) chromosomeschromosomes

Some Drosophila have irregular white eye color. When a white eye female is crossed with a normal male, the F1 generation consists of ½ normal, ½ white. The F2 generation also consists of ½ red eye and ½ white eye. WHY?

Thomas Hunt Morgan

A. Morgan’s A. Morgan’s DrosophilaDrosophila experiments experiments

Through several crosses, Morgan and his students determined that the genes for eye color were located on the X chromosome.

X

Y

chromosome complements of male & female Drosophila

Sex linked genes:Sex linked genes:members of the members of the homogametichomogametic sex (XX) have sex (XX) have two alleles per gene, members of the two alleles per gene, members of the heterogametic heterogametic sex (XY) have only sex (XY) have only oneone allele allele

Cross ACross A P: Red eye female (XP: Red eye female (X++XX++) x white eyed male (X) x white eyed male (XwwY)Y) FF11: All red eyes: All red eyes

FF22: : AllAll females red eyes, females red eyes, ½½ males white eyes males white eyes

Reciprocal cross:

Human karyotype – males are heterogametic, Human karyotype – males are heterogametic, similar to similar to DrosophilaDrosophila

Therefore, fathers pass along the genes on their X chromosome to their daughters, and they pass the Y onto their sons!

B. Pattern of Sex linked inheritanceB. Pattern of Sex linked inheritance

Genes located on the sex Genes located on the sex chromosomes are chromosomes are notnot equally inherited equally inherited by sons & daughtersby sons & daughters

sperm

eggs

X Y

X XX XY

X XX XY

Female to male ratio is 1:1

Males are Hemizygous

Sex limited & sex influencedSex limited & sex influenced

Autosomal genes responsible Autosomal genes responsible for the existence of for the existence of contrasting phenotypes, but contrasting phenotypes, but the expression of these genes the expression of these genes is dependent upon the is dependent upon the hormone constitution of the hormone constitution of the individual.individual. Sex limitedSex limited: expression is limited : expression is limited

to one gender to one gender Sex influencedSex influenced: phenotype : phenotype

expressed by a heterozygote is expressed by a heterozygote is influenced by genderinfluenced by gender

Allele appears dominant in one Allele appears dominant in one gender and recessive in the othergender and recessive in the other

men womenBB bald baldBb bald unaffectedbb unaffected unaffected

II. Human Genetics & PedigreesII. Human Genetics & Pedigrees

Geneticists are primarily interested in humans to Geneticists are primarily interested in humans to establish the pattern of transmission of inherited establish the pattern of transmission of inherited traits – specifically those associated with diseasetraits – specifically those associated with disease Mendelian ratios do not apply in individual Mendelian ratios do not apply in individual

human families because of the human families because of the small sizesmall size Controlled matings cannot be made as is Controlled matings cannot be made as is

possible in experimental geneticspossible in experimental genetics Pedigrees useful in terms of understanding the Pedigrees useful in terms of understanding the

transmission pattern of specific traitstransmission pattern of specific traits

Determining how diseases are Determining how diseases are inherited in Humans – Pedigreesinherited in Humans – Pedigrees

To determine how traits are inherited, researchers in collect To determine how traits are inherited, researchers in collect information on affected and non-affected persons in a family, information on affected and non-affected persons in a family, preparing a preparing a pedigree chart,pedigree chart, and looking for exceptions to and looking for exceptions to standard transmission patternsstandard transmission patternsPedigreePedigree = A “family tree” drawn with standard genetic = A “family tree” drawn with standard genetic symbols, showing inheritance patterns for specific phenotype symbols, showing inheritance patterns for specific phenotype characters.characters.

Used to test various hypothesis and reveal allelic determinationUsed to test various hypothesis and reveal allelic determination Determine if it is a rare inherited disorderDetermine if it is a rare inherited disorder

Pedigree:Contains info about the individuals in a family, sex, phenotype, relatedness, who is alive, twins, inbreeding, etc.

Generations in a pedigree diagram are numbered, by convention, using Roman numerals, starting with the parental generation, at the top of the diagram as generation I.

For convenience, the members of each generation are numbered across the line, from left to right, using normal numerals

Autosomal dominantboth males and females are be affectedAffected individuals appear in each generation

aa A/a

aa Aa Aa aa aa aa Aa aa

aa aa Aa aa aa

Autosomal recessive

A/a A/a

A/a

A/a A/AA/aA/A

A/-

a/a a/a

A/-

X-linked recessivemore males than females none of the offspring of an affected male are affected but all hisdaughters must be heterozygous carriers, and half the sons born to these daughters are affected

1) Autosomal1) Autosomal recessiverecessive disorders disorders

oculocutaneous albinism oculocutaneous albinism alkaptonuria alkaptonuria Bartter's syndrome Bartter's syndrome cystic fibrosis cystic fibrosis Tay-Sachs disease Tay-Sachs disease galactosaemia galactosaemia Gaucher's disease Gaucher's disease glycogen storage disease glycogen storage disease phenylketonuria phenylketonuria Wilson's disease Wilson's disease xeroderma pigmentosa xeroderma pigmentosa Sickle-cell anemiaSickle-cell anemia

2) Autosomal dominant2) Autosomal dominant disorders disorders Huntington’s diseaseHuntington’s disease Polydactyly & BrachydactylyPolydactyly & Brachydactyly Piebald spottingPiebald spotting

~290 disorders have ~290 disorders have been identified!been identified!

Red-green color Red-green color blindnessblindness

HemophiliaHemophilia Duchenne muscular Duchenne muscular

dystrophydystrophy ichythyosis ichythyosis fragile X-linked mental fragile X-linked mental

retardation retardation agammaglobulinaemiaagammaglobulinaemia

HypophosphatemiaHypophosphatemia

Xg blood group Xg blood group

Rett's syndromeRett's syndrome

4) X-linked dominant disorders

3) X-linked recessive disorders

Different types of inheritance patterns: a reviewDifferent types of inheritance patterns: a reviewSimple Mendelian – obey Mendel’s “laws”, follow strict Simple Mendelian – obey Mendel’s “laws”, follow strict dominant/recessive relationship (monohybrid F2 – 3:1)dominant/recessive relationship (monohybrid F2 – 3:1)Incomplete Dominance – occurs when the heterozygote has an Incomplete Dominance – occurs when the heterozygote has an intermediate phenotype between either corresponding intermediate phenotype between either corresponding homozygote because it is haploinsufficient (F2 – 1:2:1)homozygote because it is haploinsufficient (F2 – 1:2:1)Codominance – occurs when the heterozygote expresses both Codominance – occurs when the heterozygote expresses both alleles simultaneously and equallyalleles simultaneously and equallyLethal Alleles – an allele that has the potential for causing deathLethal Alleles – an allele that has the potential for causing deathEpistasis – occurs when the product of one gene interferes or Epistasis – occurs when the product of one gene interferes or masks the expression of another gene (F2 – 9:3:4, 12:3:1, 9:7)masks the expression of another gene (F2 – 9:3:4, 12:3:1, 9:7)X linked – involves the inheritance of genes located on the X X linked – involves the inheritance of genes located on the X chromosome. In mammals & fruit flies, males are hemizygouschromosome. In mammals & fruit flies, males are hemizygousSex influenced – refers to the impact of sex on the phenotype of Sex influenced – refers to the impact of sex on the phenotype of the individual, some alleles are dominant in one sex and recessive the individual, some alleles are dominant in one sex and recessive in the otherin the otherSex limited – refers to traits that occur only in one of the two sexesSex limited – refers to traits that occur only in one of the two sexes