Textbooks:

1. Essential Genetics By D. L. Hart & E. W. Jones (Jones & Bartlett Pub., 1999)
2. Principles of Genetics By Robert Tamarin (Wm. C. Brown Pub., 1998)

INTRODUCTION TO GENETICS

1. Definition and scope of genetics
Genetics is the study of genes, how genes regulate the production of traits or characteristics and the mechanism by which these traits are transmitted from generation to generation. Inhereted characteristics are determined by the elements of heredity that are transmitted from parents to offsprings during sexual reproduction; the elements of these hereditory determinants are called genes. Gregor Johann Mendel  in 1866 demonstrated for the first time the existance of genes and the rules that govern the transmission of genes from parents to offsprings with his experiments on inheretance in Garden Peas. In 1869 Meischer discovered DNA. But is is not until 1953 with the discovery of DNA structure by Watson and Crick that DNA was identified as the vehicle of genetic traits.
DNA is the molecule of heredity.Genetic traits can be altered by treatment with pure DNA. Transmission of DNA is the link between generations.Organisms of the same species have some traits (characteristics) in common but may differ from each other in innumberable other traits. Many of the differences between organisms result from genetic differences, the effects of the envijronment, or both. Genetics is the study of inherited traits, including those influenced in part by the environment. The elements of heredity consist of genes, which are transmitted from parents to offspring ijn reproduction. Although the sorting of genes in successive generations was first expressed numerically by Mendel, ithe chemical basis of genes was discovered by Miescher in the form of a weak acid-deoxyribonucleic acid(DNA). However, experimental proof that DNA is the genetic material did not come until about the middle of the twentieth century.
The first convincing evidence of the role of DNA in heredity came from the experiments of Avery, MacLeod, and McCarty, who showed that genetic characteristics in bacteria could be altered from one type to another by treatment with purrified DNA. In studies of Streptococcus pneumoniae, they transformed mutant cells unable to cause pneumonia into cells that could do so by treating them with pure DNA from disease-causing forms. A second important line of evidence was the Hershey- Chase experiment. Hershry and Chase showed that the T2 bacterial virus injects primarily DNA into the host bacterium (Esherichia coli) and that a much higher proportion of parental DNA, compared with parental protein, is found among the progeny.

2. The three general areas of genetics: Mendelian Genetics, Biochemical Genetics and Population Genetics

II. MENDELISM AND CHROMOSOMAL THEORY

1. Mendel’s experiments

2. Nomenclature

3. Multiple alleles

4. Genotypic interaction

 MENDELIAN GENETICS

INTRODUCTION TO MENDELIAN GENETICS LINK:

WEB link:  http://www.biology.arizona.edu/mendelian_genetics/mendelian_genetics.html
( LINK TO THE UNIVERSITY OF ARIZONA BIOLOGY RESOURCES)

The mechanism of inheretance in which the statistical relations between the distribution of characteristics (traits) in successive generations results mfrom the (1) particulate hereditory determinants currently known as genes (2) radom union of gametes (independent assorment), and (3) segregation of unchanged hereditory determinants (genes) in the gametes. Now we know that genes come in pairs (one on each homologus chromosome), separate in gametes, and join randomly in fertilization. Mendel hypothesesized that genes are particles that come in pairs. The paired genes separate (segregate) in the formation of reproductive cells. Gametes unite at random in fertilization. Genotype means genetic endowment; phenotype means traits that can be observed. Inherited traits are determined by particulate elements called genes. In a higher plant or animal, the genes are present in pairs. One member of each gene is ionherited from the maternal parent, the other from the paternal parent. A gene can have different forms that result from differences in DNA sequence. The different forms of a gene are called alleles. The particular combination of alleles pesent in an organism constitutes its genotype. The observable characterisics of an organism constitute its phenotype. In an organism, if the two alleles of a gene pair are the same( for example, AA or aa), the genotype is homozygous for the A or a allele; if the alleles are different(Aa), the genotype is heterozygous . When the phenotype of a heterozygote is the same as that of one of the homozygous genotypes, the allele that is expessed is called dominant and the hidden allele is called recessive.

The alleles of different genes segrgate independently.
The F2 genotypes in a dihybrid cross conform to Mendel's prediction. The progeny of testcrosses show the result of independent segregation. In genetic studies, the organisms produced by a mating constitute the F1 generation. Matings between members of the F1 generation produce the F2 generation . In a cross such as AAx aa, in which only one gene is considered (a monohybrid cross), the ratio of genotypes in the F2 generation is dominant homozygote (AA): 2 heterozygotes (Aa) : 1 recessive homozygote (aa). The phenotypes in the F2 generation appear in the ratio 3 dominant: 1 recessive. The Mendelian ratios of genotypes and phenotypes result from segregation in gamete formation (when the members of each alleic pair segregate into different gametes) and random union of gametes in fertilization.

The alleles of some genes do not show complete dominance.
The phenotype of a heterozygote genotype is often intermediate. In heterozygous genotypes, complete dominance of one allele over the other is nit always observed. In most cases, a heterozygote for a wildtype allele and a mutant allele that encodes a defective gene product produces less gene product than does the wildtype homozygote. If the phentype is determined by the amount of wildtype gene product rather than by its mere presence, the heterozygote will have an intermediate phenotype. This situation is called incomplete dominance. Codominance means that both alleles in a heterozygote are expressed, and so the heterozygous genotype exhibits the phenotypic characteristics of both homozygous genotypes. Codominance is exemplified by the IA and IB alleles in persons with blood group AB. Codominance is often observed for proteins when each alternative allele codes for a different amino acid replacement, because the alternative forms of the protein may be able to be distinguished by chemical or physical means. Genes are not always expressed to the same extent in different organisms; this phenomenon is called variable expressivity. A genotype that is not expressed at all in some organisms is said to have incomplete penetrance.

Chromosomes may differ in size and in postion of the centromere.

A normal chromosomes contains a single centromere, the postion of which determines the shape chromosome as it is pulled to the poles of the cell during anaphase. Rare chromosomes with no centeromeres, and those with two or more centromeres, are usually lost within a few cell generation because of aberrant separation during anaphase.
Polyploid species have multiple sets of chromosomes.
Polyploid organisms contain more than two complete sets of chromosomes. Polyploidy is widespread among higher plants but is uncommon otherwise. Between 30 and 35 percent of all species of flowering plants are thought to have originated as some form of polyploid. An autopolyploid organism contains multiple sets of chromosomes from a single ancestral species; allopolyploid organisms contain complete sets of chromosomes from two or more ancestral species. Organisms occasionally arise in which an individual chromosome is either missing (monosomic) or present in excess ( trisomic). Departures from normal gene dosage ( aneuploidy) often result in reduced viability of the zygote in animals or of the gametophyte in plants many copies of genes or chromosomes have less severe effects than too few copies. Polysomic organisms have extra or missing chromosomes.

The Results of Segregation Can Be Observed in Human Pedigrees.The Alleles of Some Genes Do Not Show Complete Dominance.

The phenotype of a heterozygous genotype is often intermediate. Biochemical tests often reveal the products of both alleles in heterozygotes. A mutant gene is not always expressed in exactly the same way.

Epistasis Can Affect the Observed Ratios of Phenotypes: Epistatis refers to interaction between nonallelic genesMore specifically epistatisis refers to a situation where genotype at one locus detemines the phenotype in such a way as to mask the genotype present at a second locus.
Complementation between Mutations of Different Genes Is a Fundamental Principle of Genetics
Lack of complementation means that two mutations are alleles of the same gene. The complementation test enables us to group mutants into allelic classes.

THE CHROMOSOMAL BASIS OF HEREDITY.

In eukaryotic cells chromosome usually are present in pairs. Each pair of chromosome seperate in meiosis, one member of each pair going to each gamete. Each Species Has a Characteristic Set of Chromosomes. The Daughter Cells produced by Mitosis Have Identical Chromosomes. Meiosis Results in Gametes That Differ Genetically

Eukaryotic Chromosomes Are Highly Coiled Complexes of DNA and Protein
Chromosome-sized DNA molecules can be separated by electrophoresis. The nucleosome is the basic structural unit of chromatin. Chromatin fibers are formed of coiled coils. Heterochromatin is rich in satellite DNA and low in gene content

The Centromere and Telomeres Are Essential Parts of Chromosome

The centromere is essential for chromosome segregation

The telomere is essential for the stability of the chromosome tips

Genes Are Located in Chromosomes

Special chromosomes determine sex in many organisms

X-linked genes are inherited according to sex

Experimental proof of the chromosome theory came from nondisjunction

Sex in Drosophila is determined by differential gene expression

LINK TO MENDELIAN TRAITS IN HUMAN:

III. MITOSIS AND MEIOSIS

WEB LINK TO: CELL REPLICATION PROCESS

1. Chromosomes

2. Mitosis

3. Meiosis

4. Meiosis in animals

5. Chromosomal theory of heredity

VI. LINKAGE AND MAPPING IN EUKARYOTES

1. Diploid mapping

2. Haploid mapping
GENE LINKAGE AND GENETIC MAPPING

Linked Alleles Tend to Stay Together in Meiosis. The frequency of recombination is the same for cis and trans heterozygotes. The frequency of recombination differs from one gene pair to the next. Recombination does not occur in Drosphlia males

Recombination Results from crossing over between Linked Alleles

Physical distance is often-but not always-correlated with map distance. Crossing-over is reciprocal and takes place at the four-strand stage. One crossover can undo the effects of another

Double Crossovers Are Revealed in Three-Point Crosses

Interference decreases the chance of multiple crossing-over

Polymorphic DNA Sequence Are Used in Human Genetic Mapping

Single-nucleotide polymorphisms (SNPs) are detected with DNA chips

Tetrads Contain All Four Products of Meiosis
Unordered tetrads have no relation to the geometry of meiosis. The geometry of meiosis is revealed in ordered tetrads
Gene conversion suggests a molecular mechanism of recombination. Recombination Results from Breakage and Reunion of DNA Molecules
V. Cytogenetics

1. Variation in chromosome structure

2. Variation in chromosome number

3. Aneuploidy in human beings
VARIATION IN CHROMOSOME NUMBER AND STRUCTURE

Chromosome differ in Size and in Position of the Centromere. Polyploid Species Have Multiple Sets of Chromosomes
Plant Cells with a Single Chromosome Set Can Be cultured. Polysomic Organisms Have Extra or Missing Chromosomes
Human Beings Have 46 Chromosomes in 23 Pairs. Down syndrome results from three copies of chromosome 21
Dosage compensation adjusts the activity of X-linked genes in females. The calico cat shows visible evidence of X-chromosome inactivation. An extra X or Y chromosome has a relatively mild effect. Amplification of a simple DNA sequence is associated with the fragile - X syndrome. Many spontaneous abortions result from chromosome abnormalities

Chromosome Rearrangements Can Have Important Genetic Effects

A chromosome with a deletion has genes missing. Rearrangements are apparent in giant polytene chromosomes
A chromosome with a duplication has extra genes. A chromosome with an inversion has some genes in reverse order
Reciprocal translocations interchange parts between chromosomes
Cancer Is Often Associated with Chromosomal Abnormalities. Transposable Elements Can Move from One Chromosome to Another

VI. LINKAGE AND MAPPING IN PROKARYOTES AND VIRUSES

1. Bacteria and virus in genetics research

2. Bacteria phenotypes

3. Viral phenotypes

4. Sexual processes in bacteria and viruses

THE GENETICS OF BACTERIA AND VIRUSES
Much of Our Understanding of Molecular Genetics Comes from Bacteria and Bacteriophages. Transformation Results from the Uptake of DNA and Recombination.In Bacterial Conjugation, DNA Transfer is Unidirectional. A plasmid is an accessory DNA molecule, usually a circle. The F plasmid can integrate into the bacterial chromosome. Chromosome transfer begins at F and proceeds in one direction. Some F plasmids carry bacterial genes
Some Phages Can Transfer Small Pieces of Bacterial DNA

Bacteriophage DNA Molecules in the Same Cell Can Recombine
Bacteriophages form plaques on a lawn of bacteria Infection with two mutant bacteriophages yields recombinant progeny
Genes are clustered by function in many bacteriophages. Recombination occurs within genes
Lysogenic Bacteriophages Do Not Necessarily Kill the Host. Specialized transducing phages carry a restricted set of bacterial genes. Bacterial Cells Contain Transposable Elements
 
 

VIII. CHEMISTRY OF THE GENE

LINK TO MOLECULAR GENETICS:

1. Nature of the genetic material

2. Nucleic acids

3. DNA replication

4. Eukaryotic DNA replication
The Structure of DNA is a Double Helix Composed of Two Intertwined Strands
The strucure of DNA is a double helix composed of two intertwined strands.
In replication, each parental DNA strand directs the synthesis of a new partner strand.
The three- dimensional structure of DNA, proposed in 1953 by Watson and Crick, gave many clues to the manner in which DNA functions as the genetic material. A molecule of DNA consists of two long chains of nucleotide subunits twisted arou nd each other to form a right-handed helix. Each nucleotide subunit contains any one of the four bases: A( adenine), T (
thymine), G (guanine), or C (cytosine). The bases are paired in the two strands of a DNA molecule: Wherever one strand has an A, the partner strand has a T; and wherever one strand has a G, the partner strand has a C. The base pairing means that the two paired strands in a DNA duplex molecule have complementary base sequences along their lengths. The structure of the DNA molecule suggested that genetic information could be coded in DNA in the sequence of bases. Mutations-- changes in the genetic material--could result from changes in the sequence of bases, such as the substitution of one nucleotide for another or the insertion or deletion of one or more nucleotides. The structure of DNA also suggested a mode of replication: The two strands of the parental DNA molecule separate, and each individual strand serves as a template for the synthesis of a new complementary strand.
Genes code for proteins. Enzyme defects result in inborn errors of metabolism. A defective enzyme results from a mutant gene.
One of the DNA strands directs the synthesis of a molecule of RNA. A molecule of RNA directs the synthesis of a polypeptide chain.
The genetic code is a triplet code.
Most genes code for proteins. More precisely stated, most genes specify the sequence of amino acids in a polypeptide chain. The transfer of genetic information from DNA into protein is a multistep process that includes several types of RNA( ribonucleic acid.) Structually, an RNA strand is similar to a DNA strand except that the "backbone" contains a different sugar (ribose instead of deoxyribose) and RNA contains the base uracil (U) instead of thymine (T). Also, RNA is usually present in cells in the form of single, unpaired strands. The initial step in gene expression is transcription, in which a molecule of RNA is synthesized that is complementary in base sequence to whichever DNA strand is being transcibed. In polypeptide synthesis, which takes place on a ribosome, the base sequence in the RNA transcript is translated in groups of three adjacent bases (codons). The codons are recognized by different types of transfer RNA (tRNA) through base pairing. Each type of tRNA is attached to a particular amino acid, and when a tRNA base-pairs with the proper codon on the mRNA, the growing end of the polypeptide chain is transferred to the amino acid on the tRNA. The table of all codons and the amino acids they specify is called the genetic code. Special codons specify the "start" (AUG,Met) and "stop" (UAA,UAG, and UGA) of polypeptide synthesis. The probable reason why various types of RNA are an intimate part of transcription and translation is that the earliest forms of life used RNA for both genetic information and enzyme catalysis.
Genes change by mutation.
A mutation that alters one or more codons in a gene can change the amino acid sequence of the resulting polypeptide chain synthesized in the cell. Often the altered protein is functionally defective, so an inborn error of metabolism results. One of thje inborn errors of metabolism studied was alkaptonuria; it results from the absence of an enzyme for cleaving homogenistic acid, which accumulates and is excreted in the urine, turning black upon oxidation. Phenylketonuria (PKU) is an inborn error of metabolism that affects the same metabolic pathway. The enzyme defect in PKU results in an inability to convert phenylalamine to tyrosine. Phenlalanine accumulation has catastrophic effects on the development of the brain. Children with the disease have severe mental deficits unless thay are treated with a special diet low in phenylalanine.Traits are affected by environment as well as by genes.Maternal PKU illustrates the importance of genes and environment.Most visable traits of organisms ressult from many genes acting together in combination with environment factors. The relationship between genes and traits is often complex because (1) every gene potentially affects many traits (pleiotropy), (2) every trait is potentially affected by many genes, and (3) many traits are significantly affected by environmental factors as well as by genes. An example of environmental effects is maternal PKU, in which mothers with a defect in phenylalanine metabolism have children with severe brain and heart abnormalities, even though their children can metabolize phenylalanine normally.
Evolution means continuity of life with change.
The molecular unity if life results from common ancestry.The diversity of life results mainly from natural selection.All living creatures are united by sharing many features of the genetic apparatus (for example, transcription and translation) and many aspects of metabolism. The unity of life results from all life being of common ancestry and provides evidence of evolution. There is also great diversity among living creatures. The three major kingdoms of organisms are the Bacteria ( which lack a membrane - bounded nucleus), the Archea ( which share features with both Bacteria and Eukarya but form a distinct group), and Eukarya (all "higher" organisms whose cells have a membrane - bounded nucleus that contains DNA organized into discrete chromosomes). Members of the kingdoms Bacteria and Archea collectively are often called prokaryotes.The ultimate source of diversity among organisms is mutation, but natual selection is the process by which mutations that enhance survival and reproduction are retained and mutations that are harmful are eliminated. Natural selection, first proposed by Darwin, is therefore the primary mechanism by which organisms become progrssively better adapted to their environments.Genetic traits can be altered by treament with pure DNA. Transmission of DNA is the link between generations

In Replication, Each Parental DNA Strand Directs the Synthesis of a New Partner Strand

Genes Code for Proteins.
Enzyme defects result in inborn errors of metabolism. A defective enzyme results from a mutant gene
One of the DNA strands directs the synthesis of a molecule of RNA. Three types of RNA are copied from the DNA; tRNA, rRNA and mRNA. A mRNA molecule directs the synthesis of a polypeptide chain

The genetic code is a triplet code

THE CHEMICAL STRUCTURE AND REPLICATION OF DNA
Complex Organisms Generally Have Large Genomes. DNA Is a Linear Polymer of Four Deoxyribonucleotides
Duplex DNA forms a Double Helix Held Together by Hydrogen Bonds. Replication Uses Each DNA Strand as a Template for a new One. Nucleotides are added one at a time to the growing end of a DNA strand. DNA replication is semiconservative. The parental strands remain intact.DNA strands must unwind to be replicated. Eukaryotic DNA molecules contain multiple origins of replication. DNA Polymerase Makes the New DNA Strands

One strand of replicating DNA is synthesized in piecec. DNA is synthesized only in the 5' - 3' direction. Each new DNA strand or fragment is initiated by a short RNA primer. Precursor fragments are joined together when they meet. Many proteins participate in DNA replication
 

XI. GENE EXPRESSION

1. Genetic Code

2. Types of RNA

3. Transcription

4. Translation

5. Eukaryotic transcription
GENE EXPRESSION
Polypeptide Chains Are Linear Polymers of Amino Acids 306. The Linear Order of Amino Acids Is Encoded in a DNA Base Sequence. The Base Sequence in DNA Specifies the Base Sequence in an RNA Transcript. The chemical synthesis of RNA is similar to that of DNA. Particular nucleotide sequences define the beginning and end of a gene. Messenger RNA directs the synthesis of a polypeptide chain

RNA Processing Converts the Orginal RNA Transcript into Messenger RNA
Splicing removes introns from the RNA transcript. Many exons code for distinct protein-folding domains. Selection of the initiation codon differs in prokaryotes and eukaryotes

The Genetic Code for Amino Acids Is a Triplet Code
Genetic evidence for a triplet code came from three - base insertions and deletions. Most of the codons were determined from in vitro poypeptide synthesis. Redundancy and near - universality are principal features of the genetic code. An aminoacyl - RNA synthetase attaches an amino acid to its tRNA. Much of the code's redundancy comes from wobble in codon - anticodon pairing. More than one polypeptide can be translated from a messenger RNA in prokaryotes. Genes can sometimes overlap
Several Ribosomes Can Move in Tandem Along a Messenger RNA

X. GENTIC ENGINEERING AND GENOME ANALYSIS

1. Restriction endonucleases

2. Vectors

3. Probing for a specific gene

4. Eukaryoric vectors

5. Restriction mapping
 

GENETIC ENGINEERING AND GENOME ANALYSIS
Cloning a DNA Molecule Takes Place in Several Steps
Restrictions enzymes cleave DNA into fragments with defined ends. Restriction fragments are joined end to end to produce recombinant DNA. A vector is a carrier for recombinant DNA. A variety of strategies can be used to clone a gene. DNA fragments are joined with DNA ligase. A recombinant cDNA contains the coding sequence of a eukaryotic gene
Loss of B - galactosidase activity is often used to detect recombinant vectors Recombinant clones are often identified by hybridization with a labeled probe

Positional Cloning Is Based on the Location of a Gene in the Genetic Map
Close genetic linkages are often conserved among related species

Reverse Genetics Creates an Organism with a Designed Mutation
Recombinant DNA can be introduced into the germ line of animals and into plant genomes

Genetic Engineering Is Applied in Agriculture, Industry, Medicine, and Research
Agricultural corp plants are primary targets of genetic engineering. Specific plant tissues can be targeted for self - destruction
Animal growth rate can be genetically engineered. Engineered microbes can help in the degradation of toxic waste
Recombinant DNA permeates modern biomedical research. The production of useful proteins is a primary impetus for recombinant DNA. Animal viruses may prove useful vectors for gene therapy. Recombinant DNA yields probes for the detection of mutant genes in hereditary disease.
An Entire Genome Can Be Physically Mapped and Its DNA Sequence Determined
The smallest complex genomes are about 100 million base pairs. Special conditions allow production and isolation of large DNA fragments. Artificial chromosomes are vectors for large DNA fragments. The landmarks in physical maps range from chromosome bands to DNA sequences

Many Large - Scale DNA Sequencing Projects Are Under Way
The complete sequence of the E.coli genome is known. The yeast genome was the first eukaryotic genome sequenced
The target date for completion of the human genome sequence is 2005

DNA Sequencing Is Highly Automated
 

Knowledge of DNA Structure Makes Possible the Manipulation of DNA Molecules
Single strands of DNA or RNA with complementary sequences can hybridizs. Restriction enzymes cleave duplex DNA at particular nucleotide sequences. Gel electrophoresis separates DNA fragments by size. Specific DNA fragments are identified by hybridization with a probe. The Polymerase Chain Reaction Makes Possible the Amplification of a Particular DNA Fragment

Chemical Terminators of DNA Synthesis Are Used to Determine the Base Sequence
The incorporation of a dideoxynucleotide terminates strand elongation. Automated DNA sequencing enables whole genomes to be analyzed Dideoxynucleotide analogs are also used in the treatment of diseases
 

XII. DNA SEQUENCING

1. Dideoxy method

2. Application of gene cloning