Primer on Medical Genomics Part II: Background Principles and Methods in Molecular Genetics

doi:10.4065/77.8.785

Mayo Clinic Proceedings

Volume 77, Issue 8, August 2002, Pages 785-808

https://doi.org/10.4065/77.8.785 Get rights and content

The nucleus of every human cell contains the full complement of the human genome, which consists of approximately 30,000 to 70,000 named and unnamed genes and many intergenic DNA sequences. The double-helical DNA molecule in a human cell, associated with special proteins, is highly compacted into 22 pairs of autosomal chromosomes and an additional pair of sex chromosomes. The entire cellular DNA consists of approximately 3 billion base pairs, of which only 1% is thought to encode a functional protein or a polypeptide. Genetic information is expressed and regulated through a complex system of DNA transcription, RNA processing, RNA translation, and posttranslational and cotranslational modification of proteins. Advances in molecular biology techniques have allowed accurate and rapid characterization of DNA sequences as well as identification and quantification of cellular RNA and protein. Global analytic methods and human genetic mapping are expected to accelerate the process of identification and localization of disease genes. In this second part of an educational series in medical genomics, selected principles and methods in molecular biology are recapped, with the intent to prepare the reader for forthcoming articles with a more direct focus on aspects of the subject matter.

Section snippets

Genes and DNA

A gene, the original Mendel “factor,”²² is the basic unit of heredity.23, 24 A gene is defined as a contiguous region of DNA25, 26 that includes a defined set of exons (protein-coding regions of DNA)²⁷ and introns (DNA regions interspersed between exons).²⁸ The basic unit of DNA is called a deoxyribonucleotide (nucleotide for short) and is made up of 1 of 4 nitrogenous bases (adenine [A], guanine [G], thymine [T], cytosine [C]) that is attached to the 1’ carbon of a deoxyribose sugar, which in

Polymerase Chain Reaction

Molecular cloning or DNA amplification often involves synthesis of multiple copies (clones) of a DNA sequence of interest (the target DNA). This may be accomplished by either inserting the target DNA into a bacterium that is capable of extended cell division (recombinant DNA technology)141, 142, 143 or using the polymerase chain reaction (PCR) for in vitro cloning of DNA (Figure 6).144, 145, 146, 147, 148 Polymerase chain reaction is an in vitro method of replicating relatively small DNA

CONCLUSION

This review on the basic principles of molecular biology is not intended to be comprehensive but to serve as an introduction to this subject. Additional information is easily accessible from numerous outstanding textbooks of molecular biology.30, 121, 270

Glossary of Terms Frequently Used in Medical Genomics

Allele: One of 2 or more alternative forms of a DNA sequence; eg, most persons have 2 functional (normal) alleles of the phenyl-alanine hydroxylase gene, whereas carriers of phenylketonuria have 1 functional allele and 1 mutant allele.
Alternative splicing: Process by which different messenger RNAs (mRNAs) are produced from the same primary transcript, through variations in the splicing pattern of the transcript.
Alu element: Short repetitive DNA sequence that is scattered throughout the genome and is

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Individual reprints of this article are not available. The entire Primer on Medical Genomics will be available for purchase from the Proceedings Editorial Office at a later date.

The authors are members of the Mayo Clinic Genomics Education Steering Committee

A glossary of terms frequently used in medical genomics appears on pages 805 through 808.

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Medical GenomicsPrimer on Medical Genomics Part II: Background Principles and Methods in Molecular Genetics

Section snippets

Genes and DNA

Polymerase Chain Reaction

CONCLUSION

Glossary of Terms Frequently Used in Medical Genomics

Trends Biotechnol

Cell

Gene

Genomics

Curr Opin Genet Dev

Biochem Biophys Res Commun

Cell

Trends Genet

Methods Cell Biol

Curr Opin Genet Dev

C R Acad Sci III

Cell

Cell

Curr Opin Struct Biol

Trends Genet

Curr Biol

Trends Biochem Sci

Curr Opin Cell Biol

Trends Biochem Sci

Curr Biol

J Biol Chem

Cell

The sequence of the human genome

Science

Initial sequencing and analysis of the human genome

Nature

Automation for genomics, part two: sequencers, microarrays, and future trends

Genome Res

Microarray technology: an array of opportunities

Nature

Biotechnology and molecular diagnostics

Forum (Genova)

Genome complexity reduction for SNP genotyping analysis

Proc Natl Acad Sci U S A

Single nucleotide polymorphisms in multiple novel thrombospondin genes may be associated with familial premature myocardial infarction

Circulation

Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling

Nature

Proteomics and its impact upon biomedical science

Br J Biomed Sci

Structural genomics offers high-speed look at proteins

Science

Structural genomics: a pipeline for providing structures for the biologist

Protein Sci

Challenges for biomedical informatics and pharmacogenomics

Annu Rev Pharmacol Toxicol

Science, medicine, and the future: bioinformatics

BMJ

Computational biology: bioinformatics—trying to swim in a sea of data

Science

Implications of the Human Genome Project for medical science

JAMA

Implications of the human genome for understanding human biology and medicine

JAMA

Genomics: are you ready for the revolution?

Nature

Bringing the human genome and the revolution in bioinformatics to the medical school classroom: a case report from Washington University School of Medicine

Acad Med

The impact of genetics on medical education and training

Br Med Bull

Ethical and legal implications of pharmacogenomics

Nat Rev Genet

Experiments in plant hybridization

Verh Naturforsch Vereines Brunn

Sex-limited inheritance in Drosophila

Science

What is a gene?

J Hered

Studies on the chemical nature of the substance inducing transformation of pneumococcal type

J Exp Med

Independent functions of viral protein and nucleic acid in growth of bacteriophage

J Gen Physiol

Genetic control of biochemical reactions in neurospora

Proc Natl Acad Sci U S A

Medical Genomics
Primer on Medical Genomics Part II: Background Principles and Methods in Molecular Genetics