X-linked and mitochondrial disorders

X-linked disorders have been historically recognized for their characteristic inheritance pattern observed in families with multiple affected males born to unaffected mothers. This type of transmission pattern and pedigree structure led to the identification of Fragile X syndrome as one of the major causes of intellectual disability in males. Mitochondrial disorders, on the other hand, have long been studied as some of the major metabolic disorders in infants due to defects in the energy-producing organelles of the cell. In this chapter, the genomic techniques that have impacted our understanding of X-linked and mitochondrial disease traits are reviewed. The challenges to consider when investigating these disorders, including incomplete X-chromosome inactivation and skewing, heteroplasmy in mitochondrial disorders, and nuclear-mitochondrial intergenomic communication are also discussed. The importance of understanding the biological pathways in which disease-associated genes are involved and regulate, and the molecular mechanisms underlying disease pathophysiology cannot be understated, as these are indispensable for molecular diagnostics and the design of targeted therapeutics for these disorders.