A planned program of study and guidance for parents of acoustically handicapped children

Thesis (Ed.M.)--Boston Universit

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Galactose-functionalised PCL nanofibre scaffolds to attenuate inflammatory action of astrocytes in vitro and in vivo

Astrocytes represent an attractive therapeutic target for the treatment of traumatic brain injury in the glial scar, which inhibits functional repair and recovery if persistent. Many biomaterial systems have been investigated for neural tissue engineering applications, including electrospun nanofibres, which are a favourable biomaterial as they can mimic the fibrous architecture of the extracellular matrix, and are conveniently modified to present biologically relevant cues to aid in regeneration. Here, we synthesised a novel galactose-presenting polymer, poly(L-lysine)–lactobionic acid (PLL–LBA), for use in layer-by-layer (LbL) functionalisation of poly(ε-caprolactone) (PCL) nanofibres, to covalently attach galactose moieties to the nanofibre scaffold surface. We have assessed the use of this novel biomaterial system in vitro and in vivo, and have shown, for the first time, the ability of galactose to maintain an attenuated inflammatory profile of astrocytes in culture, and to increase the survival of neurons after traumatic injury, as compared to control PCL nanofibres. This study highlights the importance of galactose in controlling the astrocytic response, and provides a promising biomaterial system to deliver the essential morphological and biological cues to achieve functional repair after traumatic brain injury

A Cytogenetic Abnormality and Rare Coding Variants Identify ABCA13 as a Candidate Gene in Schizophrenia, Bipolar Disorder, and Depression

Schizophrenia and bipolar disorder are leading causes of morbidity across all populations, with heritability estimates of ∼80% indicating a substantial genetic component. Population genetics and genome-wide association studies suggest an overlap of genetic risk factors between these illnesses but it is unclear how this genetic component is divided between common gene polymorphisms, rare genomic copy number variants, and rare gene sequence mutations. We report evidence that the lipid transporter gene ABCA13 is a susceptibility factor for both schizophrenia and bipolar disorder. After the initial discovery of its disruption by a chromosome abnormality in a person with schizophrenia, we resequenced ABCA13 exons in 100 cases with schizophrenia and 100 controls. Multiple rare coding variants were identified including one nonsense and nine missense mutations and compound heterozygosity/homozygosity in six cases. Variants were genotyped in additional schizophrenia, bipolar, depression (n > 1600), and control (n > 950) cohorts and the frequency of all rare variants combined was greater than controls in schizophrenia (OR = 1.93, p = 0.0057) and bipolar disorder (OR = 2.71, p = 0.00007). The population attributable risk of these mutations was 2.2% for schizophrenia and 4.0% for bipolar disorder. In a study of 21 families of mutation carriers, we genotyped affected and unaffected relatives and found significant linkage (LOD = 4.3) of rare variants with a phenotype including schizophrenia, bipolar disorder, and major depression. These data identify a candidate gene, highlight the genetic overlap between schizophrenia, bipolar disorder, and depression, and suggest that rare coding variants may contribute significantly to risk of these disorders