CHAPTER 062 PRINCIPLES OF HUMAN GENETICS PART 1

Chapter 062. Principles of Human Genetics (Part 1) Table 62-1 Selected Databases Relevant for Genomics and Genetic Disorders Site URL Comment National Center for Biotechnology Information (NCBI) http://www.ncbi.nlm.nih.gov/ Molecular biology information, public databases, compu[r]

Chapter 062. Principles of Human Genetics (Part 1) Harrison's Internal Medicine > Chapter 62. Principles of Human Genetics Impact of Genetics on Medical Practice Impact of Genetics on Medical Practice: Introduction The beginning of the new millennium was marked by the announcem[r]

Chapter 062. Principles of Human Genetics (Part 18) Phenotypic Heterogeneity Phenotypic heterogeneity occurs when more than one phenotype is caused by allelic mutations (e.g., different mutations in the same gene) (Table 62-4). For example, laminopathies are monogenic multisystem disorders t[r]

Chapter 062. Principles of Human Genetics (Part 24) Nucleotide Repeat Expansion Disorders Several diseases are associated with an increase in the number of nucleotide repeats above a certain threshold (Table 62-6). The repeats are sometimes located within the coding region of the genes, as i[r]

Chapter 062. Principles of Human Genetics (Part 9) Nucleic Acid Hybridization Nucleic acid hybridization is a fundamental principle in molecular biology that takes advantage of the fact that the two complementary strands of nucleic acids bind, or hybridize, to one another with very high spec[r]

Chapter 062. Principles of Human Genetics (Part 10) Transgenic Mice as Models of Genetic Disease Several organisms have been studied extensively as genetic models, including Mus musculus (mouse), Drosophila melanogaster (fruit fly), Caenorhabditis elegans (nematode), Saccharomyces cerevisiae[r]

Chapter 062. Principles of Human Genetics (Part 12) The Genetic Map Given the size and complexity of the human genome, initial efforts aimed at developing genetic maps to provide orientation and to delimit where a gene of interest may be located. A genetic map describes the order of genes an[r]

Chapter 062. Principles of Human Genetics (Part 13) The Human DNA Sequence The complete DNA sequence of each chromosome provides the highest resolution physical map. The primary focus of the HGP was to obtain DNA sequence for the entire human genome as well as model organisms. Although the p[r]

Chapter 062. Principles of Human Genetics (Part 14) Transmission of Genetic Disease Origins and Types of Mutations A mutation can be defined as any change in the primary nucleotide sequence of DNA regardless of its functional consequences. Some mutations may be lethal, others are less delete[r]

Chapter 062. Principles of Human Genetics (Part 22) Inherited mitochondrial disorders are transmitted in a matrilineal fashion; all children from an affected mother will inherit the disease, but it will not be transmitted from an affected father to his children (Fig. 62-11D ). Alterations in[r]

Chapter 062. Principles of Human Genetics (Part 15) Unequal Crossing-Over Normally, DNA recombination in germ cells occurs with remarkable fidelity to maintain the precise junction sites for the exchanged DNA sequences (Fig. 62-3). However, mispairing of homologous sequences leads to unequal[r]

Chapter 062. Principles of Human Genetics (Part 25) Complex Genetic Disorders The expression of many common diseases such as cardiovascular disease, hypertension, diabetes, asthma, psychiatric disorders, and certain cancers is determined by a combination of genetic background, environmental[r]

Chapter 062. Principles of Human Genetics (Part 16) Dipyrimidine and CPG Sequences Certain DNA sequences are particularly susceptible to mutagenesis. Successive pyrimidine residues (e.g., T-T or C-C) are subject to the formation of ultraviolet light–induced photoadducts. If these pyrimidine[r]

Chapter 062. Principles of Human Genetics (Part 30) DNA testing is performed by mutational analysis or linkage studies in individuals at risk for a genetic disorder known to be present in a family. Mass screening programs require tests of high sensitivity and specificity to be cost-effective[r]

Chapter 062. Principles of Human Genetics (Part 17) Genotypes describe the specific alleles at a particular locus. For example, there are three common alleles (E2, E3, E4) of the apolipoprotein E (APOE) gene. The genotype of an individual can therefore be described as APOE3/4 or APOE4/4 or a[r]

Chapter 062. Principles of Human Genetics (Part 20) Figure 62-9 Figure 62-10 Segregation of alleles. Segregation of genotypes in the offspring of parents with one dominant (A) and one recessive (a) allele. The distribution of the parental alleles to their offspring depends on the combinatio[r]

Chapter 062. Principles of Human Genetics (Part 19) Penetrance refers to the proportion of individuals with a mutant genotype that express the phenotype. If all carriers of a mutant express the phenotype, penetrance is complete, whereas it is said to be incomplete or reduced if some individu[r]

Chapter 062. Principles of Human Genetics (Part 8) Transcriptional activation can be divided into three main mechanisms: 1. Events that alter chromatin structure can enhance the access of transcription factors to DNA. For example, histone acetylation generally opens chromatin structur[r]

Chapter 062. Principles of Human Genetics (Part 7) Transcriptional Activation and Repression Every gene is controlled uniquely, whether in its spatial or temporal pattern of expression or in its response to extracellular signals. It is estimated that transcription factors account for ~30% of[r]

Chapter 062. Principles of Human Genetics (Part 28) Allelic Association, Linkage Disequilibrium, and Haplotypes Allelic association refers to a situation in which the frequency of an allele is significantly increased or decreased in individuals affected by a particular disease in comparison[r]