Neet PG Biochemistry MCQS-4

A 8-month-old girl presents to hematology clinic after her 9-month checkup showed anemia. Her serum iron and transferring levels were normal, and her hemoglobin electrophoresis demonstrated an abnormal hemoglobin in addition to A and A2. Which of the following represents the most likely change at her β-globin locus and the genetic process that produced it? (Recall that the normal β-globin locus has the gene order Gγ-Aγ-δ-β.)

1.Gγ-Aγ-δ-β,Unequal recombination
2.Gγ-Aγ-δ-β fusion,unequal recombination
3.Gγ-Aγ- deletion B,gene conversion
4.Gγ-Aγ-deletion-B gene conversion
5.Gγ-Aγ-β-deletion,gene conversion

Solution:

Gene recombination during chromosome synapsis at the first and second meiotic divisions produces unique genetic constitutions in each gamete and derived conception. In the first meiotic division, the chromosomes are tetraploid and recombination occurs mostly between sister chromatids of the same chromosome. In the second meiotic division, recombination may occur between chromosome homologues. Recombination is normally “equal,” meaning that the crossover of DNA strands is at the same base pair on each chromosome arm and produces no excess or deficient DNA. Among chromosome regions with repetitive DNAs, including gene families like the globins that are similar in sequence, it is common to have “unequal” crossovers with mismatched pairing. The child with anemia proved to have hemoglobin Lepore (141900), produced by unequal recombination between a δ-globin gene on one chromatid and a β-globin gene on the other. The child therefore had normal fetal hemoglobin produced from α- and γ-globin genes, but produced an abnormal hemoglobin due to δβ-globin gene fusion on one chromosome. The reciprocal antiLepore recombination would be lost at meiosis II, and the child would have a normal β-globin locus on the chromosome 11 received from the other parent. This produces a mild to moderate anemia once the switch occurs from fetal to adult hemoglobin at 3–6 months.