Since the discovery that DNA alterations initiate tumorigenesis, scientists and clinicians have been exploring ways to counter these changes with targeted therapeutics. The sequencing of tumor DNA was initially limited to highly actionable hot spots—areas of the genome that are frequently altered and have an approved matched therapy in a specific t...
The same mutation can have different effects in different individuals. One important reason for this is that the outcome of a mutation can depend on the genetic context in which it occurs. This dependency is known as epistasis. In recent years, there has been a concerted effort to quantify the extent of pairwise and higher-order genetic interaction...
This article describes my experiences over more than 50 years in initiating and maintaining research on human genetics and genomics at the National Research Centre in Cairo, Egypt, from its beginnings in a small unit of human genetics to the creation of the Center of Excellence for Human Genetics. This was also the subject of a lecture I gave at th...
Facioscapulohumeral muscular dystrophy (FSHD), a progressive myopathy that afflicts individuals of all ages, provides a powerful model of the complex interplay between genetic and epigenetic mechanisms of chromatin regulation. FSHD is caused by dysregulation of a macrosatellite repeat, either by contraction of the repeat or by mutations in silencin...
Many traits of interest are highly heritable and genetically complex, meaning that much of the variation they exhibit arises from differences at numerous loci in the genome. Complex traits and their evolution have been studied for more than a century, but only in the last decade have genome-wide association studies (GWASs) in humans begun to reveal...
Published in Annual Review of Genomics and Human Genetics
Over the last decade, a rich variety of massively parallel assays have revolutionized our understanding of how biological sequences encode quantitative molecular phenotypes. These assays include deep mutational scanning, high-throughput SELEX, and massively parallel reporter assays. Here, we review these experimental methods and how the data they p...
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that affects multiple organ systems due to an inactivating variant in either TSC1 or TSC2, resulting in the hyperactivation of the mechanistic target of rapamycin (mTOR) pathway. Dysregulated mTOR signaling results in increased cell growth and proliferation. Clinically, TSC patients...
Transcription activator-like effectors (TALEs) from the genus Xanthomonas are proteins with the remarkable ability to directly bind the promoters of genes in the plant host to induce their expression, which often helps bacterial colonization. Metaphorically, TALEs act as spies that infiltrate the plant disguised as high-ranking civilians (transcrip...
Sooty blotch and flyspeck (SBFS) fungi produce superficial, dark-colored colonies on fruits, stems, and leaves of many plant genera. These blemishes are economically damaging on fruit, primarily apple and pear, because they reduce the sale price of fresh fruit. Fungicide spray programs can control SBFS but are costly and impair human and environmen...
Gram-positive bacteria are prominent members of plant-associated microbial communities. Although many are hypothesized to be beneficial, some are causative agents of economically important diseases of crop plants. Because the features of Gram-positive bacteria are fundamentally different relative to those of Gram-negative bacteria, the evolution an...
