Organization of Genetics Course Molecular Genetics Cytogenetics Transmission Genetics Population Genetics

Molecular Genetics Identification of DNA as the genetic material Structure of DNA Function of Genes Gene (DNA) RNA PROTEIN Gene Regulation Mutation and Genetic Variation (origin of alleles) Linking diseases to specific alleles Genetic Technologies Genetic testing Gene Therapy

Genomics Identification, sequencing and mapping of all human genes Evolution of the human genome

Cytogenetics Meiosis Chromosome Theory of Inheritance Karyotypes Identification of Chromosome Abnormalities

Transmission Genetics Mendelian Principles Alleles, Dominant/Recessive Genotype Determines Phenotype Extensions to Mendelian Principles Multiple alleles Lethal alleles Additive alleles Co-dominance Partial dominance Epistasis Linkage and Genetic Mapping

Population Genetics Mendelian and Molecular Genetics of Populations Frequency of alleles (e.g., “disease” alleles) How allele frequency changes over time DNA Fingerprinting p 2 + pq + q 2 = 1

Normal Red Blood Cell Sickle Cell Anemia Red Blood Cell

Hemoglobin

Allele (DNA) RNA Protein Genotype/Phenotype

N C Fig. 13-1, Page 307 Flow of Genetic Information

DNA Structure 5’ 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 Anemia Red Blood Cell

ATG GTG CAC TTG ACC CCC GAG GAG met - val - his - leu - thr - pro - glu - glu 5’ 3’ (N) (C) Hb A 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) Hb A Hb S Molecular Genetics of Sickle-Cell Anemia HbA HbS

Pg. 350 Fig. 350

Hemoglobin

Healthy Lung Lung epithelial cells Lung epithelial cells

Lung epithelial cells Lung epithelial cells 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 epithelial cells Lung epithelial cells AA or Aa

Lung epithelial cells Lung epithelial cells Cystic Fibrosis Lung aa

Chromosome genes 158 million bp of DNA CFCTR Gene

Chromosome genes 158 million bp of DNA CFCTR Genotype AA A A Phenotype Healthy

Chromosome genes 158 million bp of DNA CFCTR Genotype Aa A a Phenotype Healthy

Chromosome genes 158 million bp of DNA CFCTR Genotype aa a a Phenotype Cystic Fibrosis

Huntington’s Disease

Cell from “Hh” individual Huntingtin protein aggregates

Trinucleotide Repeat Diseases

Fig Pg. 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 Genetic testing weeks Fig Pg. 555

Early Embryonic Development (~ 7 days)

8 cell Embryo from IVF Remove one cell for genetic testing Pre-Implantation Genetic Diagnosis

Genetic Testing for Sickle Cell Anemia Embryos Made by IVF Parents Hb S Hb A Fig Pg. 556

Genetic Testing for Sickle Cell Anemia Embryos Made by IVF Parents Implant embyro #1 Hb S Hb A Fig Pg. 556

Early Embryonic Development (~ 7 days)

Fig Pg. 559

Microarray (“gene chip”) Normal B-Cell Purify mRNA Label mRNA with “green” dye Diffuse Large B-Cell Lymphoma Purify mRNA Label mRNA with “red” dye Hybridize to Microarray

DLBCL Individuals Microarray Analysis of Diffuse Large B-Cell Lymphoma Genes (~ 18,000)

Gene Therapy for Severe Combined Immunodeficiency Fig Pg. 561 “aa” individual “aa” cells Virus with “A” allele “Aaa” cells Cloned “A” allele

DNA Sequencing: How it works Products separated By gel electrophoresis Fig Pg. 477

Fig Pg. 486

“Raw” DNA sequence Where are the genes?

Fig Pg. 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 Pg. 497

Gene Genes comprise ~ 5% of genome Repeated DNA comprises ~ 50% of genome Unique (“junk”) DNA comprises the rest Organization of Human Genome Fig Pg. 494 (~ 50 kbp)

Comparative Genomics Pg. 499

Genome Transcriptome Proteome All of the DNA of a cell Methods: 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. 9-7 Pg. 219

13 proteins encoded by human mitochondrial genome

Heteroplasmy Mutant Normal

Interphase and M-Phase Chromosomes

Chromosome genes 158 million bp of DNA

Histone Structure

Fig. 12-9

Interphase and M-Phase Chromosomes

Core Promoter Fig. 17-4

Leucine Zipper Transcription Factor DNA Binding Domain Activation Domain Fig

Formation of the Pre-initiation Complex Fig