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 ReviewClassical Mendelian GeneticsDNA and ChromosomesMolecular GeneticsImmunity and CancerGenetic Counseling, Gene Therapy,

EthicsPopulation/Evolutionary Genetics

Grading

Lab Work (Lab participation and reports, Lab questions,) 35%

Lecture quizzes 30%Final Exam 20%Family Tree 10%Problem sets 10%Class participation 5%

1. DNA

2. Gene

4. Genome

5. Individual

3. Chromosome7. Population

6. Family (pedigree)

Cell

Disorder Defective protein

Phenotype

Achondroplasia Growth factor receptor

Dwarfism

Cystic fibrosis Chloride transporter

Lung, digestive pathology

Duchenne’s muscular dystrophy

Dystrophin Muscle function

Hemophilia Factor VIII Blood clotting defect

Familial Hypercholesterolemia

LDL receptor High cholesterol, heart disease

Human Mendelian Disorders

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.

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

Genome

• Consists of 3 billion base pairs of DNA

• Includes 28,000 to 34,000 genes

• Is organized as 23 pairs of chromosomes

The Human Genome

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.

Inheritance of traits can be observed in families.A pedigree indicates the structure of a family schematically.

Family

A population is a group of interbreeding individuals who possess a particular collection of alleles or “gene pool”.

Population

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

QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.

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 allelesof 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 observingincidence 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 possibleDifferent populations have different

characteristic frequenciesCorrection of the underlying genetic

defect may be possible

Our First Assignment

Developing a family history according to recommendations of the American Society of Human Genetics.

Building a pedigree of some trait using that pedigree to consider whether it could have a genetic component.

Unaffected MaleUnaffected FemaleAffected male Affected female

Parents

Offspring

Pedigree Analysis

Human Pedigree Symbols

Disease

No disease

Assuming pedigrees like this are available (they never are), how do youfind 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

An Ideal(ized) Pedigree

Royal Pedigree of Porphyria

Geneology DNA Testing

http://www.familytreedna.com/