The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Parkinson's Disease: Basic Pathomechanisms and a Clinical Overview

PD is a common and a debilitating degenerative movement disorder. The number of patients is increasing worldwide and as yet there is no cure for the disease. The majority of existing treatments target motor symptom control. Over the last two decades the impact of the genetic contribution to PD has been appreciated. Significant discoveries have been made, which have advanced our understanding of the pathophysiological and molecular basis of PD. In this chapter we outline current knowledge of the clinical aspects of PD and the basic mechanistic understanding

Production and Characterization of Monoclonal Antibodies to Human Sclerostin

We developed and characterized monoclonal antibodies directed against the amino-terminal and carboxy-terminal regions of human and mouse sclerostin (scl). Amino-terminal and carboxy-terminal scl peptides with limited homology to scl domain-containing protein-1 were synthesized using f-moc chemistry. The peptides were conjugated to keyhole limpet hemocyanin and the conjugates were used for immunization of mice. Monoclonal antibodies were obtained and characterized using bacterially expressed and insect cell–expressed recombinant scl. The amino-terminal (IgG 2aK) and carboxy-terminal (IgG 2bK) antibodies bound bioactive sclerostin that was expressed in an insect-cell expression system with dissociation constants in the nanomolar range. The antibodies are potentially useful agents that can be used for modulating sclerostin bioactivity

Collecting, Comparing, and Computing Sequences: The Making of Margaret O. Dayhoff’s Atlas of Protein Sequence and Structure, 1954–1965

Collecting, comparing, and computing molecular sequences are among the most prevalent practices in contemporary biological research. They represent a specific way of producing knowledge. This paper explores the historical development of these practices, focusing on the work of Margaret O. Dayhoff, Richard V. Eck, and Robert S. Ledley, who produced the first computer-based collection of protein sequences, published in book format in 1965 as the Atlas of Protein Sequence and Structure. While these practices are generally associated with the rise of molecular evolution in the 1960s, this paper shows that they grew out of research agendas from the previous decade, including the biochemical investigation of the relations between the structures and function of proteins and the theoretical attempt to decipher the genetic code. It also shows how computers became essential for the handling and analysis of sequence data. Finally, this paper reflects on the relationships between experimenting and collecting as two distinct ‘‘ways of knowing’’ that were essential for the transformation of the life sciences in the twentieth century