Deep Sequencing of the Pedigree Reveals the Extensive Nature of Genetic Recombination. The illustrated chromosome is vertically split to depict the inheritance state from the father (P, left half) and the mother (M, right half) based on nucleotide sequencing of the genomes of the parents and the two children in the pedigree. Mendelian inheritance patterns can be grouped into four states for each polymorphic nucleotide position with children receiving one of the following: a) the same allele from both the father and the mother (identical); b) the same allele from the mother but the opposite allele from the father (haploidentical maternal); c) the same allele from the father but opposite from the mother (haploidentical paternal); and d) opposites from both parents (non-identical). In the illustration, the pattern of inheritance is shown in blocks, with the dark blocks representing regions of recombination that occurred in the parental germ line during meiosis. In areas where a light blue segment abuts a dark blue segment, the siblings are haploidentical (paternal or maternal). In areas where a dark blue segment abuts a dark blue segment, the siblings are non-identical. Only in those regions in which light blue portions of the schematic karyotype are adjacent are the siblings effectively twins. Overall, 22 percent of the siblings’ genomes were found to be identical. This finding markedly narrowed the area that needed to be searched for the disease-causing mutations (red horizontal lines), as a recessive inheritance pattern was suggested to account for both Miller syndrome and primary ciliary dyskinesia.

Deep Sequencing of the Pedigree Reveals the Extensive Nature of Genetic Recombination. The illustrated chromosome is vertically split to depict the inheritance state from the father (P, left half) and the mother (M, right half) based on nucleotide sequencing of the genomes of the parents and the two children in the pedigree. Mendelian inheritance patterns can be grouped into four states for each polymorphic nucleotide position with children receiving one of the following: a) the same allele from both the father and the mother (identical); b) the same allele from the mother but the opposite allele from the father (haploidentical maternal); c) the same allele from the father but opposite from the mother (haploidentical paternal); and d) opposites from both parents (non-identical). In the illustration, the pattern of inheritance is shown in blocks, with the dark blocks representing regions of recombination that occurred in the parental germ line during meiosis. In areas where a light blue segment abuts a dark blue segment, the siblings are haploidentical (paternal or maternal). In areas where a dark blue segment abuts a dark blue segment, the siblings are non-identical. Only in those regions in which light blue portions of the schematic karyotype are adjacent are the siblings effectively twins. Overall, 22 percent of the siblings’ genomes were found to be identical. This finding markedly narrowed the area that needed to be searched for the disease-causing mutations (red horizontal lines), as a recessive inheritance pattern was suggested to account for both Miller syndrome and primary ciliary dyskinesia.

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