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Additional resources for Biochemistry and Genetics Pretest Self-Assessment and Review
Rapid parallel sequencing is enabling panels of genes (eg, those causing X-linked mental disability or autism) to be tested, now culminating in the ability to screen the expressed regions of all genes for mutations (exome sequencing). Non-Mendelian inheritance mechanisms include mitochondrial inheritance (exhibiting maternal transmission), expansion of triplet repeats (exhibiting anticipation in pedigrees as in the fragile X syndrome), High-Yield Facts in Biochemistry and Genetics 47 Chromosome analysis (karyotype) FIuorescent In Situ hybridization (FISH) array-comparative genomic hybridization (aCGH, microarray analysis) β–globin gene Ε1 11 Ε2 12 Ε3 E = exons; I = introns DNA RNA 1 2 3 4 5 6 NNNNNNNNN-ATG-GTG-CAC-CTG-ACT-GAG– hgb A Northern blotting (rarely used clinically) Detection of specific microRNAs Protein GTG val met-val-his-leu-thr-glu— hgb A hgb S β β β α α α s s β α hgb S DNA (gene analysis) a) Southern blotting to measure gene segment sizes b) PCR amplification of gene segments and DNA sequencing to detect mutant alleles or DNA markers c) Exome DNA sequencing-analysis of multiple genes culminating in whole genome sequencing Protein analysis a) Protein function—enzyme assays, hemoglobin oxygenation curves b) Protein structure— electrophoresis, Western blotting c) Protein profiling to define variants conveying risks (personalized medicine) Figure 19 The molecular hierarchy and levels of genetic analysis showing (from top to bottom): a representative chromosome diagram, a chromosome segment, a specific gene (β-globin) with exons (E) and exons (I), the β-globin DNA sequence mutated to produce sickle hemoglobin (S), its derived amino acid substitution and globin tetramers, and the resulting normal and sickled red blood cells.
Irreparable damage halts cell cycle progression and initiates cell death (apoptosis). The tumor suppressor gene p53, mutated in Li-Fraumeni tumor syndrome and several human cancers, has a key role in G1/G2 checkpoint controls. Figure 15 DNA replication fork demonstrating asymmetry with continuous DNA polymerization (long arrow) on the leading strand and discontinuous DNA polymerization/ligation of Okazaki fragments on the lagging strand (short arrows). The asymmetry is necessary for unidirectional replication along antiparallel DNA strands because nature provides only 5′ to 3′ DNA polymerases.
The basal metabolic rate (BMR) measures body energy requirements at rest, assessed at 12 hours after feeding (morning); charts accounting for weight, age, and gender allow calculation of BMR rather than direct measurement. • Vigorous activity, hypermetabolic states (AIDS, cancer), and protein catabolism after trauma or inflammatory illnesses can increase the BMR up to eightfold (with skiing, stair climbing, and jogging); intake of calories above those needed to maintain the BMR causes the individual to be overweight (BMI >25) or obese (BMI >30), where the BMI (body mass index) is weight in kilograms divided by height in meters squared.
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