Human Genetics
Introduction
Human genetics: Why?
Determine genotypic basis of variant
phenotypes to facilitate:
 Understanding biological basis of human
genetic diversity
 Prenatal diagnosis
 Predictive testing
 Development of intelligent therapies
 Correction of genetic defects
 Human Identification for forensics, evolution
Class Objectives
1. To provide an understanding of the basic
principles of genetics.
2. To provide an understanding of the genetic
basis of human disease and current
approaches to treatment and prevention of
genetic disorders.
3. To relate the study of human genetics to major
advances in molecular genetics and
biotechnology.
4. To provide an awareness of the interaction
between genetic and environmental factors
underlying birth defects and the development of
human disease.
Class Objectives
5. To relate human genetics to current issues in
genetic screening, genetic counseling and
genetic engineering.
6. To provide an awareness of the relationship of
the individual genome to the genetic makeup of
the human population and its ramifications to
human diversity.
7. To provide a learning opportunity for students
enrolled in Biological and Health Sciences
applicable to career areas including biomedical
technology, pre-medical, secondary education,
special education, and nursing.
Course Topics
Cell Biology and Biochemistry Review
Classical Mendelian Genetics
DNA and Chromosomes
Molecular Genetics
Immunity and Cancer
Genetic Counseling, Gene Therapy,
Ethics
Population/Evolutionary Genetics
2. Gene
Cell
1. DNA
4. Genome
3. Chromosome
5. Individual
6. Family (pedigree)
7. Population
Human Mendelian Disorders
Disorder
Defective
protein
Phenotype
Achondroplasia
Growth factor
receptor
Dwarfism
Cystic fibrosis
Chloride
transporter
Lung, digestive
pathology
Duchenne’s muscular
dystrophy
Hemophilia
Dystrophin
Muscle function
Factor VIII
Blood clotting defect
Familial
Hypercholesterolemia
LDL receptor
High cholesterol,
heart disease
Multifactorial Disorders
Breast Cancer
Biopolar affective disorder
- manic depression
Dyslexia
Diabetes mellitus
- adult onset & obesity
Hypertension
Neural tube defects
- folic acid
Schizophrenia
- 1% affected
Seizure disorders
Genetic Technology
What is Genetics?
Genetics is the study of heredity and its
variation.
Human genetics: What's different?
 Nothing (in principle)
 Unmatched by other organisms for
phenotypic complexity
Genes are DNA
• Genes are the basic unit of inheritance.
• Genes are composed of DNA (deoxyribonucleic acid)
• Genes direct the formation of proteins.
Different versions of the same gene are called
alleles.
Alleles result from the process called mutation.
All genes are nucleic acids (RNA and DNA) but not
all nucleic acids are genes.
Somatic versus Germline Cells
Somatic cells comprise the majority of an
individual’s body.
• During development distinct types of cells
make proteins using different subsets of genes.
Germline cells within the testis or ovary produce
gametes (sperm or ovum)
• Germline cells retain the ability to form all of
the types of cells, both germline and somatic cells.
Together somatic cells and germline cells
comprise the entire body of an individual.
Genome
The complete set of genetic information
characteristic of the organism.
The genome includes:
• All of the genes present in an organism and
• Other DNA sequences that do not encode genes
The Human Genome
• Consists of 3 billion base pairs of DNA
• Includes 28,000 to 34,000 genes
• Is organized as 23 pairs of chromosomes
Individuals
Individuals carry two alleles of each gene.
Genotype is the combination of alleles that an
individual possesses.
Phenotype is the visible trait that results from a
particular genotype.
Family
Inheritance of traits can be observed in families.
A pedigree indicates the structure of a family
schematically.
Population
A population is a group of interbreeding
individuals who possess a particular collection
of alleles or “gene pool”.
Species Comparisons
Comparison of DNA sequences indicates the
amount of similarity between two species.
98% of human DNA sequences are shared with
chimpanzee.
Many genes present in humans are also
present in mice, fish, fruit flies, yeast, and
bacteria.
Humans are very similar
On average, two random
people share the same
DNA sequence in 99.9%
of their genome.
Studies of variation
indicate humans arose in
Africa and migrated
across the globe with
relatively little change.
Humans are also very different
On average two
random people differ
at 3 million base pairs
(approximately one
nucleotide of every
thousand).
A few genes can have
a big impact on
appearance.
Understanding the relationship between
genotype and phenotype
1) Experimental
organisms: manipulate
genotype, determine
phenotype
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2) Humans: assay
phenotypes, determine
genotype (statistics)
How are traits determined?
Traits can be determined predominantly by one
gene.
Mendelian traits result from variation in alleles
of one gene.
Traits can be determined by multiple genes.
Polygenic traits result from variation in
several genes.
Traits can be determined by genes and
environment.
Multifactorial traits result from effects of one
or more genes and the environment.
Genetic Risk
Absolute risk
the probability that an individual will
develop a condition or trait
Relative risk
the likelihood that an individual from
one group will develop a condition in
comparison to another group
(usually the general population)
Empiric risk
risk determined by observing
incidence of a trait in the population
Risk factor
a situation that alters incidence of a
disease (or trait)
Brief History
Human Genome Decoded 2001
How Genetic Diseases Differ from
Other Diseases
One can predict recurrence risk in other
family members
Predictive testing is possible
Different populations have different
characteristic frequencies
Correction of the underlying genetic
defect may be possible
Pedigree Analysis
Parents
Offspring
Unaffected Male
Unaffected Female
Affected male
Affected female
Human Pedigree Symbols
An Ideal(ized) Pedigree
Disease
No disease
Assuming pedigrees like this are available (they never are), how do you
find linked molecular markers (and clone the gene)?
1) Obtain polymorphic markers for loci that "span the genome"
2) Identify closely linked flanking markers
3) Narrow non-recombinant interval and test candidates for causality
Royal Pedigree of Porphyria
Geneology DNA Testing
http://www.familytreedna.com/