Chapter 15: The chromosomal basis of inheritance Chromosome Theory of inheritance Chromosome Theory of inheritance Genes have specific loci on chromosomes Genes have specific loci on chromosomes Chromosomes undergo segregation & independent assortment Chromosomes undergo segregation & independent assortment Thomas Hunt Morgan Thomas Hunt Morgan Worked with Drosophila melanogaster (fruit fly) Worked with Drosophila melanogaster (fruit fly) 4 pairs of chromosomes; 3 autosomes; 1 pair of sex chromosomes 4 pairs of chromosomes; 3 autosomes; 1 pair of sex chromosomes Notation w + (wild type) w - (mutant type) Notation w + (wild type) w - (mutant type)

Drosophila melanogaster

Variation in fruit fly red eye (wild type) vs. white eye (mutant)

Sex-linked traits Genes located on the sex chromosomes Genes located on the sex chromosomes Males more likely to inherit sex linked traits; only one mutant allele required for trait (XY vs. XX female) Males more likely to inherit sex linked traits; only one mutant allele required for trait (XY vs. XX female) Provides evidence for specific genes being located on specific chromosomes Provides evidence for specific genes being located on specific chromosomes

Linked genes & genetic recombination Genes on the same chromosome at close loci tend to be inherited together Genes on the same chromosome at close loci tend to be inherited together Recombinants= offspring which exhibit non-parental phenotypes Recombinants= offspring which exhibit non-parental phenotypes When 50% frequency of recombinants exist genes are located on different chromosomes When 50% frequency of recombinants exist genes are located on different chromosomes When recombinant frequency is less than 50% genes are located on the same chromosome; recombinants result from crossing over; amount of recombinants is related to the distance between the two gene’s loci When recombinant frequency is less than 50% genes are located on the same chromosome; recombinants result from crossing over; amount of recombinants is related to the distance between the two gene’s loci

Linkage mapping Genetic map Genetic map Ordered list of gene loci along a chromosome Ordered list of gene loci along a chromosome Higher frequency of recombinants=bigger distance between 2 loci Higher frequency of recombinants=bigger distance between 2 loci Provide positional information of loci only in relation to other loci Provide positional information of loci only in relation to other loci Linkage map Linkage map Genetic map based on recombination frequencies Genetic map based on recombination frequencies Cytogenetic maps Cytogenetic maps Locate genes on a chromosome based on chromosome features such as banding Locate genes on a chromosome based on chromosome features such as banding Ultimate maps Ultimate maps Show physical distance between loci in DNA nucleotides Show physical distance between loci in DNA nucleotides

Concept Check Genes A, B, & C are located on the same chromosome. Testcrosses show that the recombination frequency between A & B is 28% and between a & C is 12%. What possible linear orders exist between these genes? Genes A, B, & C are located on the same chromosome. Testcrosses show that the recombination frequency between A & B is 28% and between a & C is 12%. What possible linear orders exist between these genes?

Sex-linked Genes

X A = normal gene X a = mutated gene

Human sex-linked disorders Duchenne Muscular Dystrophy Duchenne Muscular Dystrophy Defective dystrophin protein Defective dystrophin protein Leads to weakened muscles & loss of coordination Leads to weakened muscles & loss of coordination Hemophilia Hemophilia Absence of one or more proteins required for clotting in blood Absence of one or more proteins required for clotting in blood Prolonged bleeding Prolonged bleeding Color-blindness Color-blindness

X inactivation in Female mammals One chromosome from a pair of chromosomes becomes inactivated during embryonic development One chromosome from a pair of chromosomes becomes inactivated during embryonic development Inactive chromosome condenses into Barr body Inactive chromosome condenses into Barr body Lies on inner edge of nuclear envelope Lies on inner edge of nuclear envelope Genes on Barr body are typically not expressed Genes on Barr body are typically not expressed Barr body formation is independent event in each cell Barr body formation is independent event in each cell Methyl groups attached to DNA to cause inactivation Methyl groups attached to DNA to cause inactivation

Concept Check A white eyed female Drosophila is mated with a red eyed male. What phenotypes & genotypes would be likely in the offspring? A white eyed female Drosophila is mated with a red eyed male. What phenotypes & genotypes would be likely in the offspring? Neither Tom nor Rhoda has Duchenne Muscular Dystrophy but their first born son does. What is the probability that their second child will have the disease? Neither Tom nor Rhoda has Duchenne Muscular Dystrophy but their first born son does. What is the probability that their second child will have the disease?

Disorders caused by chromosome alteration Non-disjunction Non-disjunction Pairs of homologues do not separate during meiosis Pairs of homologues do not separate during meiosis Aneuploidy-abnormal number of a particular chromosome Aneuploidy-abnormal number of a particular chromosome Trisomy Trisomy monosomy monosomy Polyploidy- two complete chromosome sets Polyploidy- two complete chromosome sets Common in plants Common in plants Can occur in animals though rare Can occur in animals though rare Likely to look normal in appearance Likely to look normal in appearance

Disorders caused by chromosome alteration Alterations in chromosome structure Alterations in chromosome structure Deletion Deletion Chromosome fragment is lost; certain genes are missing Chromosome fragment is lost; certain genes are missing Duplication Duplication Deleted fragment attaches as an extra segment to a homologous chromosome Deleted fragment attaches as an extra segment to a homologous chromosome Inversion Inversion Deleted fragment re-attaches to orginal chromosome but in reverse orientation Deleted fragment re-attaches to orginal chromosome but in reverse orientation Translocation Translocation Deleted fragment attaches to a non-homologous chromosome Deleted fragment attaches to a non-homologous chromosome

Human disorders due to chromosomal alteration Down Syndrome (Trisomy 21) Down Syndrome (Trisomy 21) Non-disjunction in meiosis leads to mental retardation, characteristic features Non-disjunction in meiosis leads to mental retardation, characteristic features Klinefelter syndrome Klinefelter syndrome XXY; sterile male with some female characteristics (i.e. breasts) XXY; sterile male with some female characteristics (i.e. breasts) Turner syndrome Turner syndrome XO; sterile female XO; sterile female Cri-du-chat syndrome Cri-du-chat syndrome Deletion on chromosome 5 leads to mental retardation, characteristic features & cry sounding like a cat Deletion on chromosome 5 leads to mental retardation, characteristic features & cry sounding like a cat Chronic myelogenous leukemia Chronic myelogenous leukemia Translocation between chromosomes 22 & 9 Translocation between chromosomes 22 & 9

Down Sydrome Klinefelter Syndrome

Cri-du-chat

Concept Check How could a male can have the tortoiseshell phenotype? How could a male can have the tortoiseshell phenotype?

Genomic imprinting Effect of a gene may be dependant on whether gene was inherited from mother or father Effect of a gene may be dependant on whether gene was inherited from mother or father Methyl group is added to one of the alleles in the gamete to cause inactivation (or in a few cases activation) Methyl group is added to one of the alleles in the gamete to cause inactivation (or in a few cases activation) Zygote expresses only one allele of an imprinted gene; this same allele is the active gene in all resulting cells Zygote expresses only one allele of an imprinted gene; this same allele is the active gene in all resulting cells

Inheritance of organelle genes Some genes located outside the nucleus (extranuclear genes) Some genes located outside the nucleus (extranuclear genes) Mitochondria Mitochondria chloroplasts chloroplasts Organelles located in zygote originate in egg (egg has more cytosol); all extranuclear genes originate from the mother Organelles located in zygote originate in egg (egg has more cytosol); all extranuclear genes originate from the mother