Introduction

The hemoglobinopathies resulting from mutations in the a- or p-globin gene clusters are the most common singlegene disorders in humans. An estimated 7% of the world population carries one or more globin gene mutations[1] and over 300,000 persons each year are born with a severe hemoglobinopathy. Although most of the more than 700 identified hemoglobin variants are clinically inconsequential, several different single nucleotide substitutions lead to critical amino acid substitutions that cause hemolytic anemia, i.e., sickle cell disease (SCD), unstable hemoglobins, or hemoglobin tetramers that have altered oxygen affinity.

These variant hemoglobins have featured prominently in the development of molecular medicine and genomic and proteomic diagnostics. Pauling's investigations on hemoglobin in sickle cell anemia were the first demonstration of a causal link between an inherited alteration in protein molecular structure and a disease. In 1985, SCD also was the first genetic disease involving a point mutation in a single-copy gene to which diagnostic Southern blotting was applied, i.e., hybridization of genomic DNA with allele-specific oligonucleotide probes.

Heterozygosity for clinically significant hemoglobin variants (e.g., HbS, HbC, and HbE), as is the case for thalassemias and glucose-6-phosphate dehydrogenase (G6PD) deficiency, confers advantage in malarial endemic regions. This hypothesis was first formulated by Haldane, and the complex interrelationships among genetics, ecology, and culture on the frequency of sickle cell disease (SCD) were later established by the anthropologist Livingstone.1-2-1 Subsequent research on genetic drift and gene flow supports the proposition that an introduction of agriculture several thousand years ago promoted malarial endemicity and exerted evolutionary selection on hemo-globinopathies.[3] In historic malarial belt high-risk populations, different globin chain abnormalities (hemoglobin variants and thalassemias) often interact to produce marked hemolytic anemia or red blood cell (RBC) sickling. Structural hemoglobinopathies that cause anemia also complicate pregnancy by increasing risk of intrauterine growth restriction, preterm birth, low birth weight, and perinatal mortality.[4]

Getting Started With Dumbbells

Getting Started With Dumbbells

The use of dumbbells gives you a much more comprehensive strengthening effect because the workout engages your stabilizer muscles, in addition to the muscle you may be pin-pointing. Without all of the belts and artificial stabilizers of a machine, you also engage your core muscles, which are your body's natural stabilizers.

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