Lecture Notes for General Biology BI 101 - Genetics


Nobel Prize Updates

I Genetics - History

	A) Primitive civilizations - domestication of plants and animals, important
		demonstration of early genetic engineering, lead to agricultural development
	B) 1800's: 
		1)Mendel - laid down the foundation for the field of genetics
	C) early 1900's:
		1) Morgan uses fruit flies, identifies chromosomes as region of cell
			where genes are stored in the cell
		2) DeVries describes the first mutations in plants - rediscovers Mendel's
			work
	D) Modern Genetics - practical applications
		1) Populations Genetics - Evolution
		2) Oncology, oncogenes and Cancer
		3) Genetic Disease and Gene Therapy
		4) Recombinant Technology (e.g., crop resistance, animal breeding, etc...)
		5) DNA Fingerprinting
			a) Human applications
			b) Wildlife Management and illegal importation 
			of endangered species


II Genetics - Mendelian Inheritance and beyond Mendel

	A) Definition
		1) study of inheritance = transmission of traits from one generation
			to the next
	B) Mendel's experiments - experimental design
		1) subject = pea plants
		2) traits = flower color (purple, white), flower position (axial, terminal),
			seed color (yellow, green), seed shape (smooth, wrinkled), pod
			color (yellow, green), pod shape (inflated, constricted)
		3) controlled breeding experiments
			a) paint brush and scissors (to remove stamens) = tools
				Stamen - male part of the plant that produces pollen
				Carpel - female part of the plant that produces eggs
			b) matings: pure x pure, like x unlike, offspring
			c) example - monohybrid cross
	C) Mendel's contributions
		1) different morphological traits come in two's 
		(e.g., smooth or wrinkled seed), must be 2 particles 
			inside the cell that determine the
			morphological trait, alleles = alternative forms 
			of a gene
		2) always 2 particles in the adult (2N) = genes 
		composed of 2 alleles
		3) Relationships exists between alleles, most 
		common is dominance 
		4) Law of segregation - alleles segregate on gametes
		5) Law of independent assortment, two genes 
				assort independently on the gametes
		6) Modern terminology - Genes and Alleles
			a) two alleles = A (dominant), a (recessive) (A > a)
			b) three combinations of genes from two alleles = AA, Aa, aa
				AA = homozygote dominant
				aa = homozygote recessive
				Aa = heterozygote
			c) Phenotype = trait caused by the gene (two alleles)
				P = purple flower, p = white flower
				PP, Pp = purple flowers
				pp  = purple flowers
			d) Punnett Square and making gametes
		7) Mendel's experiments 
			Results of various phenotypes and their corresponding genotypes

			Monohybrid cross - example of flower color (P - purple, p - white)
			3 generations - P, F1, F2
Generation Male Female
P PP pp
     
Punnett Square for P Female gametes Female gametes
Male gametes p p
P Pp Pp
P Pp Pp
     
Results Offpsring of P Males Females
  Pp Pp
Phenotypic Ratio 100% Dominant, Purple flowers  
Genotypic Ratio 100% Pp  
     
 
Generation Male Female
F1 Pp Pp
     
Punnett Square for P Female gametes Female gametes
Male gametes P p
P PP Pp
p Pp pp
     
 
F2 Generation    
Phenotypic Results - Offpsring of F1 Purple flowers White Flowers
Individuals PP, Pp, Pp pp
% 3/4 = 75% 1/4=25%
Phenotypic Ratio = 3:1 3 1
Genotypic Results Offpsring of F1 PP Pp pp
  PP Pp, Pp pp
  1/4 2/4 1/4
% 25% 50% 25%
Genotypic Ratio= 1:2:1 1 2 1

3 Types of Monohybrid crosses

Homozygous Dominant x Homozygous Dominant (similar results with recessive x recessive)

AA x AA

Gametes A A
A AA AA
A AA AA
Results    
Phenotypic Ratio 100% Dominant  
Genotypic Ratio 100% AA  

 

Homozygous dominant x Heterozygote

AA x Aa

Gametes A a
A AA Aa
A AA Aa
Results    
Phenotypic Ratio

AA - dominant phenotype

AA - dominant phenotype

Aa - dominant phenotype

Aa - dominant phenotype

 

4 dominant phenotypes/4 offspring = 100%

 

100% Dominant

 
Genotypic Ratio

2 homozygous dominants (AA)/4 offspring = 50%

2 heterozygotes (Aa)/4 offspring = 50%

1 (AA):1 (Aa)

 

 

Homozygous recessive x Heterozygote

aa x Aa

Gametes A a
a Aa aa
a Aa aa
Results    
Phenotypic Ratio

Aa - dominant phenotype

Aa - dominant phenotype

aa - recessive phenotype

aa - recessive phenotype

 

2 dominant phenotypes/4 offspring = 50%

2 recessive phenotypes/4 offspring = 50%

 

1 dominant phenotype : 1 recessive phenotype

 
Genotypic Ratio

2 homozygous recessives (aa)/4 offspring = 50%

2 heterozygotes (Aa)/4 offspring = 50%

1 (aa):1 (Aa)

 

 

Heterozygote x Heterozygote

Aa x Aa

Gametes A a
A AA Aa
a Aa aa
Results    
Phenotypic Ratio

AA - dominant phenotype

Aa - dominant phenotype

Aa - dominant phenotype

aa - recessive phenotype

 

3 dominant phenotypes/4 offspring = 75%

1 recessive phenotype/4 offspring = 25%

 

3 (Dominant): 1 (recessive)

 
Genotypic Ratio

1 homozygous dominant (AA)/4 offspring = 25%

2 heterozygotes (Aa)/4 offspring = 50%

1 homozygous recessive (aa)/4 offspring = 25%

1 (AA) :2 (Aa):1 (aa)
 


			Dihybrid cross - example
Generation Y - yellow seed, y - green seed, R - round seed, r - wrinkled seed  
P YYRR x yyrr  
F1 YyRr x YyRr  
F2 = ? solution - break it up into two heterozygous crosses  
  Yy x Yy Rr x Rr
Gametes Y y Gametes R r
Y YY Yy R RR Rr
y Yy yy r Rr rr
Results    
Phenotypic Ratio for Monohybrid Crosses

YY - dominant phenotype - yellow

Yy - dominant phenotype - yellow

Yy - dominant phenotype - yellow

yy - recessive phenotype - green

 

3 dominant phenotypes (yellow)/4 offspring = 3/4 = 75%

1 recessive phenotype (green)/4 offspring = 1/4 = 25%

 

3 (Dominant) yellow: 1 (recessive) green

RR - dominant phenotype - round

Rr - dominant phenotype - round

Rr - dominant phenotype - round

rr - recessive phenotype - wrinkled

 

3 dominant phenotypes (round)/4 offspring = 3/4 = 75%

1 recessive phenotype (wrinkled)/4 offspring = 1/4 = 25%

 

3 (Dominant) round: 1 (recessive) wrinkled

Phenotypic Ratio for Dihybrid Crosses

Possible Phenotypes (probability)

Probabilities
Yellow (3/4) round (3/4)
(3/4)(3/4)=9/16
Yellow (3/4) wrinkled (1/4)
(3/4)(1/4)=3/16
Green (1/4) round (3/4)
(1/4)(3/4)=3/16
Green (1/4) wrinkled (1/4)
(1/4)(1/4)=1/16
 

E) Beyond Mendel

1) More than two alleles for a phenotype

a) Human blood groups - A, B, O

2) Relationships between genes -Epistasis

a) one gene masks the presence of another

b) hypothetical example of coat color B - black and dominant over b -brown C - color deposition and dominant over c - no color

Genotype Phenotype
BBCC black coat
BbCc black coat
bbCC brown
bbCc brown
Bbcc brown (black turned off by cc)
BBcc brown (black turned off by cc)

		3) Expression of the phenotype is affected by the 
			environment
			a) tanning, bleaching of hair, shaving, stunted 
			trees near treeline
		4) Codominance
			a) human blood groups (A, B, O)
		5) Incomplete dominance
			a) snapdragons (Red x White = some red, some white, 
			some pink plants)
		6) Continuous variation and polygenic inheritance
			 Distribution of data 
      7) Pleiotropy - one allele contributes information to 2 or more phenotypes

III The Chromosomal Basis of Inheritance

	A) 3 Questions
		1) Where are genes and alleles located?
		2) How are they arranged?
		3) How are they transmitted from one generation to the next?
	B) Search for genetic material - Genes on Chromosomes
                Morgan's study of Fruit Flies
                        Eye color is sex-linked


Punnett Square

P Generation: X+X+ (pure wild) x XY (white eye males)

Gametes X Y
X+ X+X X+Y
X+ X+X X+Y
Results    
Phenotypic Ratio 100% Dominant - wild/red-eye  

 

F1 Generation X+X (wild heterozygote) x X+Y (wild males)

Gametes X+ Y
X+ X+X+ X+Y
X XX+ XY
Results = F2 Generation    
Phenotypic Ratio

X+X+, X+Y, XX+

3 wild/red-eye

XY

1 (white-eye) male

    no white-eye females


	C) Arrangement
		1) Alleles are located on homologous chromosomes
			site of the allele is the locus
	D) Transmission of genes from generation to the next
		1) Meiosis is the mechanisms, generates variation 
			based on how the homologous chromosomes line up 
			across from each other during Metaphase I
		2) Other chromosome alterations occur during 
			transmission
			a) inversions 
			b) deletions
			c) crossing over
	E) Sex determination and Chromosomes
Organism XX XY Other
Human female male  
Bird male female  
Grasshopper female   male X_ (no Y chromosome)
Bee    

diploid female

haploid male

	F) Karyology - study of chromosome number
		process - karyotyping

V Chemical Basis of Inheritance

	A) Makeup of Chromosomes
		Proteins - histones
		DNA coiling
	B) Genetics code in Proteins or DNA?
		1) Griffiths
			Smooth and rough strains of bacteria
		2) Hershey-Chase
			labeling radioisotopes and viruses
		3) Watson and Crick (and Rosalind) describe double-helix
			Components of the Double Helix
				Nucleotide
					Phosphate, Sugar and Nitrogenous base
				Nitrogenous Bases 
					Purines
						Adenine (A) and Guanine (G)
					Pyrimidines
						Cytosine (C) and Thymine (T)
				Bonds
					A bonds with T
					C bonds with G
	C) Arrangement of chemicals on the chromosome
		histones - proteins for DNA coiling
		non-coding DNA
		coding DNA
			introns and exons			
	D) DNA replication
		semi-conservative model
	E) Making proteins/enzymes from information in DNA - Transcription and Translation
		Genes make proteins for biochemical reactions inside cell
			One gene one enzyme hypothesis
				Evidence - Garrod and alkaptonuria
				Evidence - Beadle and Tatum, neurospora mold
		Transcription in the nucleus
			extracting information with mRNA
		Translation at rough ER - uses codons from mRNA and anticodons from tRNA
			mRNA interacts with tRNA
			tRNA contains Amino Acids
	F) Transposons - jumping genes
		Barbara McLintock discovered them in corn			

VI Genetic Disease - Practical Applications

	A) Genetic diseases - occur at two levels
		1) genic
		2) chromosomes
		3) Links to online resources on Genetic Disease
			Hereditary Disease Foundation
			Human Genetics: A Resource for Teachers
			Genetic Disorder Corner from the Genetic Science Learning Center at the University of Utah
	B) Diseases at the level of the gene (genic mutations)
		Recessive Disorders (homozygote recessive aa)
		1) Hemophilia - blood clotting problems, victims bleed to death 
			a) due to recessive allele - sex-linked
		2) Sickle-cell anemia - lack proper blood proteins and RBC's are
			sickle shaped versus normal, unable to carry O2 efficiently, causes various symptoms
				a) due to recessive allele
				causes a simple substitution
		3) Phenylketonuria - unable to produce enzymes to breakdown
			chemicals in diet soda, can lead to toxic buildup and death,
			check the warning on diet soda cans!!
			a) due to recessive allele
		4) Galactosemia - unable to produce enzymes necessary for breakdown
				of galactose in milk, toxic buildup
			a) due to recessive allele
			b) Links to galactosemia web sites
				Galactosemia.com
				Information from the American Liver Foundation
			c) Galactosemia is not lactose intolerance (not a genetic disease, occurs over time and with aging)
				Information from NDDIC
				Information from NIH
		5) Lesch-Nyhan disease - missing an enzyme necessary for purine metabolism, leads to
				hyperpuricemia, severe mental retardation, self-mutilation and renal failure
				X-linked recessive disease
		Dominant Disorders (homozygote dominant AA and heterozygote Aa)
		6) Huntington's Disease - deterioration of nervous system
			a) due to dominant allele
		7) Achondroplastic dwarfism - small stature, disproportionate limbs, short broad hands and feet, waddling gait
			a) due to dominant allele
			b) affects bone growth beginning at birth
			c) usually does not affect intelligence but psychological problems may occur when child realizes he/she is different
		8) Familial hypercholesterolemia - causes severe elevation in total cholesterol and LDL, leads to high risk of CHD
			(coronary heart disease), problem occurs with malfunctioning LDL receptor proteins that affects LDL uptake
		9) Mechanism - substitution of nitrogenous bases
			a) example: CAC mutates to CCC, A replaced by C, changes genetic
				information and results in production of ineffective proteins
	C) Syndromes and Chromosomal disorders
			Overview
		Extra chromosomes
		1) Klinefelter's Syndrome - XXY sex chromosomes, sterile males,	
			may show some female features
		2) XYY Syndrome - extra Y in males
			a) individuals exhibit normal development and above average height,tendency to delayed mental maturation 
				with an increased probability for learning problems 
		3) Metafemales - XXX, normal development and sexual characteristics, usually taller than other females with 
			some learning difficulties
		4) Down's Syndrome (Down Syndrome, Trisomy, Trisomy 21) - extra chromosome 21 , results in mental
			retardation, heart defects, more likely to occur in infants born to older women
		Missing chromosomes
		5) Tuner's syndrome - X_, females lack one X chromosome, some mental retardation
			results in sterility, short in stature, never develop ovaries, increased incidence of thyroid problems
		6) Mechanism
			a) Non-disjunction during meiosis, some gametes contain extra 
				chromosome, other gametes are missing chromosome
		7) Good link with summary of sex chromosome abnormalities
	D) Chromosomal rearrangements and Genetic Disease
		1) Deletions
			a)  Cri du Chat syndrome, broken chromosome  results 
				in retardation, malformed larynx and vocal problems
			b) Fragile X Syndrome - broken chromosome results in sterility
				mental retardation, oversized testes in males, double-
				jointedness
	E) Methods of Detection
		Pedigree analysis
			legend of terms
			actual pedigree
		Monitoring levels of chemicals in the blood
		CVS - chroionic villus sampling
		Amniocentesis

V DNA Technology 

	A) Recombinant Technology - genetic engineering
		1) splicing genes from one organism into another organism

 	B) Techniques
		1) viral transfer - using viruses to transfer genes
		2) restriction enzymes and plasmids in bacteria
		3) gene gun and microprojectiles - small ‘DNA coated’ pellets shot into the cell at high speed. 
		4) bacterial transformation and plants
			bacterial DNA
			plasmids
			bateria and transformation
		5) Liposomes - small spheres with foreign DNA attach to and fuse with the cell membrane, 
			DNA enters host cyptoplasm
		6) Electroporation - host cell is shocked with small, rapid bursts of electrical currents which
				create gaps in the cell membrane and permit entry of foreign DNA
		7) DNA injection with small micropipette (micromanipulator) used to inject DNA into host cell
	C) Why splice genes from one organisms into another - Treat Disease
		1) Drugs and hormones produced by recombinant bacteria
			a) Using microbes to produce hormones or enzymes that individuals
				with genetic diseases can not make for themselves
				1) Splice normal human genes into bacteria which will
					make the desired product, involves using restriction enzymes 
					which cut the desired DNA sequence which is  spliced on to bacteria chromosomes
				2) examples - Human growth hormone, insulin, interferon, 
					Factor VIII, vaccines
				3) Summary table 
		4) Gene therapy/replacement
			a) defective genes are replaced with normal genes, works for
				some genetic diseases, in the experimental stages
			b) Cystic Fibrosis - defect in the CF transmembrane regulator (CFTR) gene that controls electrolyte (e.g., salts) transport in 
				in the lung, pancreas, GI tract, current research on inhaling viruses with the genes to correct salt problem
				in lung cells, liposomes also used to transfer normal genes into cells
			c) SCID - WBC's are removed and cultured,infected with viruses 
				containing normal genes, reintroduced back into the body
			d) Hemophilia - Greengard et al. (1997) reported success in dogs with hemophilia
					dogs missing clotting factor received new genes to produce clotting factor
					and were producing clotting factor 18 months later
			e) Familial hypercholesterolemia - working on LDL receptor protein, abnormal liver cells
				removed and exposed to viruses with genes for LDL recptor protein, new liver cells with
				gene from virus reintroduced into liver, LDL was lowered
			f)  Gaucher's disease - inability to break down lipids that accumulate in the spleen, marrow, liver, 
				and sometimes in the brain, high incidence in Ashkenazi Jews, autosomal recessive disorder,
				occurs in Macrophages (WBCs), stem cells are harvested and these cells receive new gene in cell culture 
				from retroviruses, the new stem cells are put back into the patient where they go to the bone marrow and give rise
				to new macrophages with the new genes
			h) Application for treating cancer - suicide genes used to kill brain tumor cells, inject tumor
				cells in vivo with retrovirus containing suicide gene, then treat patient with acyclovir that kills cells
	D) Why splice genes from one organisms into another - Agriculture
			Various transgenic organisms: plants, mice,
		1) Examples of transgenic plants with resistance to viruses
			a) Tomato, potato and tobacco 
		2) Examples of transgenic plants with resistance to insects
			a) cotton, corn 
		3) resistance to herbicides
		4) retard spoilage in tomatoes
		5) Supreme example - strawberry
			a) resistance to drought, salt tolerance, insects, viruses, 
				cold and frost, taste

VI Other Current Research in DNA Technology

	A) DNA analyses and Genetic Fingerprinting
		1) DNA fingerprinting in the courtroom
			a) Comparison of variable fragment lengths (RFLP's), cut by
				restriction enzymes, comparisons are made by
				running electrophoretic gels
				stain DNA or proteins on the gels
				comparing the bands
		2) PCR ability to make copies from small samples
		3) DNA and Wildlife Management
			a) Protection of Endangered Wildlife and Poaching
				1) Project to describe DNA of all big game species
					for comparison with suspicious meat from
					poachers or importers - genetic database
				2) National Fish and Wildlife Forensics Laboratory
		4) Identifying the remains of soldiers missing or killed in action
			a) Department of Defense web site
	B) DNA Sequencing - Human Genome Project
		Goals
		1) Create a map of genes located on human chromosomes
				Examples - Chromosome viewer
		2) identify all human genes (estimates from 30,000 - 100,000)
	`	3) list the nucleotide sequence (A,T,C,G) for all human DNA
		4) decsribe amount and degree of genetic variation among humans
		5) consider and or illustrate ethical, legal, social issues concerning this information and how it
			should/can be used
		Current knowledge
		1) We have about 30,000 - 40,000 genes
		2) 95% of the DNA is non-coding DNA (repetitive sequences)
		3) We share many genes with other organisms (from Yeast to Fruit Flies to Chimps)
		4) Gene discovery - normal bodily functions, genetic diseases
	C) Cloning: Dolly
			a) First clones - tadpoles using embryonic cells and nuclear transfer
			b) Today - many organisms (sheep, cattle, mice, rabbits, pigs, goats, cats)  using nuclear transfer
					and artifical twining
			c) Why clone
					1) produce cloned animals to produce proteins to treat disease (milk in goats, sheep)
					2) produce cloned and transgenic animals for organ transplantation
					3) cloning extinct and endangered species
						Mouflon Lamb in Corsica and Sardinia
					4) pet cloning
					5) therapeutic human cloning and stem cells
			d) Cloning Webliography
			e) Overview of the process 
					overview from the Roslin Institute
					endangered species model

BI 01 Homepage

Saint Anselm College Homepage

Blackboard at Saint Anselm College

Dr. Jay's Homepage

 

Trademark and Disclaimers

Copyright © 2001 Jay Pitocchelli. All rights reserved. The contents of this page are the intellectual property of Dr. Jay Pitocchelli for distribution to students enrolled in General Biology BI 01 at Saint Anselm College. These pages may not be copied, photocopied, reproduced, translated, or published in any electronic or machine-readable form in whole or in part without prior written approval of Jay Pitocchelli. Students enrolled in General Biology BI 01 at Saint Anselm College have permission to print this material for their lecture notes. The images linked to this web page are the sole property of Addison Wesley/ Benjamin Cummings Publishers™.