Organization of Genetics Course

Molecular Genetics

Cytogenetics

Transmission Genetics

Population Genetics

Molecular GeneticsIdentification of DNA as the genetic materialStructure of DNAFunction of Genes

Gene (DNA) RNA PROTEINGene Regulation

Mutation and Genetic Variation (origin of alleles)Linking diseases to specific allelesGenetic Technologies

Genetic testingGene Therapy

GenomicsIdentification, sequencing and mapping of all human genesEvolution of the human genome

CytogeneticsMeiosisChromosome Theory of InheritanceKaryotypesIdentification of Chromosome Abnormalities

Transmission GeneticsMendelian Principles

Alleles, Dominant/RecessiveGenotype Determines Phenotype

Extensions to Mendelian PrinciplesMultiple allelesLethal allelesAdditive allelesCo-dominancePartial dominanceEpistasisLinkage and Genetic Mapping

Population GeneticsMendelian and Molecular Genetics of Populations

Frequency of alleles (e.g., “disease” alleles)How allele frequency changes over timeDNA Fingerprinting

p2 + pq + q2 = 1

Normal Red Blood Cell

Sickle Cell AnemiaRed Blood Cell

Hemoglobin

Allele (DNA) RNA Protein

Genotype/Phenotype

N CFig. 13-1, Page 307

Flow of Genetic Information

DNA Structure5’

3’ 5’

3’

Fig. 1-8,Page 5

Fig. 13-7,Page 314

Possible Reading Frames for RNA

Fig. 13-7,Page 314

Normal Red Blood Cell

Sickle Cell AnemiaRed Blood Cell

ATG GTG CAC TTG ACC CCC GAG GAG

met - val - his - leu - thr - pro - glu - glu

5’ 3’

(N) (C)

HbA

Molecular Genetics of Sickle-Cell Anemia

HbA

ATG GTG CAC TTG ACC CCC GAG GAG

met - val - his - leu - thr - pro - glu - glu

5’ 3’

(N) (C)

ATG GTG CAC TTG ACC CCC GTG GAG

met - val - his - leu - thr - pro - val - glu

5’ 3’

(C)(N)

HbA

HbS

Molecular Genetics of Sickle-Cell Anemia

HbA

HbS

Pg. 350Fig. 350

Hemoglobin

Healthy Lung

Lung epithelialcells

Lung epithelialcells

Lung epithelialcells

Lung epithelialcells

Cystic Fibrosis Lung

Chloride Ion Channel gene and protein involved in Cystic Fibrosis

Missense mutation

Nonsense mutation

Frame-shift mutation

Deletion, in-frame

CFCTR Gene

Mutations

Healthy Lung

Lung epithelialcells

Lung epithelialcells

AAorAa

Lung epithelialcells

Lung epithelialcells

Cystic Fibrosis Lung

aa

Chromosome 7

1367 genes158 million bp of DNA

CFCTR Gene

Chromosome 7

1367 genes158 million bp of DNA

CFCTR GenotypeAA

A A

PhenotypeHealthy

Chromosome 7

1367 genes158 million bp of DNA

CFCTR GenotypeAa

A a

PhenotypeHealthy

Chromosome 7

1367 genes158 million bp of DNA

CFCTR Genotypeaa

a a

PhenotypeCystic Fibrosis

Huntington’s Disease

Cell from “Hh” individual

Huntingtin protein aggregates

Trinucleotide Repeat Diseases

Fig. 19-2Pg. 459

Restriction Enzymes

Chloride Ion Channel gene and protein involved in Cystic Fibrosis

Missense mutation

Nonsense mutation

Frame-shift mutation

Deletion, in-frame

CFCTR Gene

Mutations

Amniocentesis

Genetictesting 14-16 weeks

Fig. 22-8Pg. 555

Early Embryonic Development (~ 7 days)

8 cell Embryo from IVF

Remove onecell for genetic testing

Pre-Implantation Genetic Diagnosis

Genetic Testing for Sickle Cell Anemia

EmbryosMade by IVF

Parents

HbS

HbA

Fig. 22-9Pg. 556

Genetic Testing for Sickle Cell Anemia

EmbryosMade by IVF

Parents

Implant embyro #1

HbS

HbA

Fig. 22-9Pg. 556

Early Embryonic Development (~ 7 days)

Fig. 22-14Pg. 559

Microarray(“gene chip”)

Normal B-CellPurify mRNALabel mRNA with “green” dye

Diffuse Large B-Cell LymphomaPurify mRNALabel mRNA with “red” dye

Hybridize to Microarray

DLBCLIndividuals

Microarray Analysis of Diffuse Large B-Cell Lymphoma

Genes (~ 18,000)

Gene Therapy for Severe Combined Immunodeficiency

Fig. 22-10Pg. 561

“aa” individual

“aa” cells

Virus with “A” allele

“Aaa” cells

Cloned “A” allele

DNA Sequencing: How it works

Products separatedBy gel electrophoresis

Fig. 19-28Pg. 477

Fig. 20-1Pg. 486

“Raw” DNA sequence

Where are the genes?

Fig. 20-2Pg. 488

ORF scanning in all reading frames and both strands

ORFs are in brown

Fig. 13-7,Page 314

Pg. 494

Function of Human Genes

Fig. 20-13Pg. 497

Gene Gene GeneGene Gene

Genes comprise ~ 5% of genomeRepeated DNA comprises ~ 50% of genomeUnique (“junk”) DNA comprises the rest

Organization of Human Genome

Fig. 20-8Pg. 494

(~ 50 kbp)

Comparative Genomics

Pg. 499

Genome

Transcriptome

Proteome

All of the DNA of a cellMethods: DNA sequencing, computer analysis

All of the mRNA produced by a cell

Method: Microarray analysis (gene chips)

All of the proteins produced by a cell

Methods: 2-dimensional gel eletrophoresis

Eukaryotic Cell

Electron Micrograph of Mitochondrial DNA

Fig. 9-7Pg. 219

13 proteins encodedby human mitochondrialgenome

HeteroplasmyMutant

Normal

Interphase and M-Phase Chromosomes

Chromosome 7

1367 genes158 million bp of DNA

Histone Structure

Fig. 12-9

Interphase and M-Phase Chromosomes

Core Promoter

+1-25-80-120

Fig. 17-4

Leucine Zipper Transcription Factor

DNA Binding Domain

ActivationDomain

Fig. 17-16

Formation of the Pre-initiation Complex

Fig. 17-11