特定疾病的项目|Overview
See the latest results for some of these projects on ourASHG Meeting page.
Atopic Dermatitis
Investigators
Lynda Schneider, MD(首席研究员)
Ingrid A. Holm, MD, MPH
Louis M. Kunkel, PhD
Isaac Kohane, MD, PhD
Atopic dermatitis (AD), a type of eczema, is the most common chronic skin disorder of childhood, estimated to affect more than 10 percent of children worldwide. Its incidence is increasing, and most children with AD develop other atopic diseases including food allergy, allergic rhinitis and asthma. This project is phenotyping patients with AD, identifying variants in known and novel genes that may be associated with AD and investigating genetic and environmental risk factors, as well as gene-environment interactions. Currently Boston Children’s Hospital is following approximately 12,000 children with AD.More information on the atopic dermatitis project on ClinicalTrials.gov.
Autism Spectrum Disorder
Investigators
Louis M. Kunkel, PhD(首席研究员)
Christopher Walsh, MD, PhD(首席研究员)
Leonard Rappaport, MD
Ingrid A. Holm, MD, MPH
Isaac Kohane, MD, PHD
Autism spectrum disorder (ASD)由严重的社会，语言和认知障碍表现出来，包括一系列遗传相关的疾病，包括自闭症，普遍发育障碍，否则指定了（PDD-NOS）和阿斯伯格障碍。尽管遗传力估计超过90％，但ASD的明显遗传原因是难以捉摸的。这项研究是对ASD及其家人的儿童进行行为和身体表型，试图将这种疾病细分为更均匀的群体，以增加我们检测相关基因和基因途径的能力。
To do this, we are investigating differences in gene expression in patients’ white blood cells, as well as investigatingrare, recessive forms of autism. Our approaches include transmission disequilibrium testing (TDT), affected sib pair (ASP) analysis, genomic sequencing,RNA表达研究and novel Bayesian algorithms (which utilize all data both from phenotypic analysis and from expression arrays).
These studies could lead to a biologically based diagnosis of ASD, a better understanding of the disease process and possible novel interventions. The gene expression research has led to ablood test for autismthat is now in clinical development.
Congenital Myopathies
Investigator
The congenital myopathies are rare genetic conditions that cause muscle weakness, sometimes life-threatening. Some children have symptoms at birth, while others develop weakness in childhood or adulthood that impairs walking, breathing and feeding. With the goal of eventually developing effective therapies, this project seeks to better understand the genes and proteins involved in the congenital myopathies by identifying new candidate genes, screening affected patients, developing phenotype/genotype correlations, and exploring gene and protein expression in affected muscle. Expression analysis methods include microarray analysis and functional studies. Our focus includes centronuclear/myotubular myopathy, congenital fiber type disproportion, multiminicore myopathy, nemaline myopathy, and other congenital myopathies as yet undefined. Once we identify a gene, we canmodel its effects in zebrafishand screen potential drugs.
For more information,visit the Beggs Laband read coverage on our science blog,Vector:
- Gene therapy strengthens weak muscles in congenital myopathy
- Restoring muscle function in a rare, devastating disease(2 part series)
Developmental Disorders of the Brain
Investigator
The Walsh Lab is working to uncover the fundamental cellular and genetic mechanisms directing the development of the cerebral cortex, the largest structure of the human brain. Genetic mutations can alter specific steps of brain development and lead to abnormal brain structure or function, resulting from atypical cell growth, accumulation of cells in abnormal locations in the brain and/or defects in cell function.
Conditions we are interested in include microcephaly, lissencephaly, polymicrogyria and heterotopia, which can be visualized by magnetic resonance imaging (MRI) of the brain and can cause epilepsy, intellectual disability and/or autism. By studying people affected with these conditions and identifying the associated genes and their mutations, we are learning more about the proteins that are important for brain development. It is hoped that this will lead to better diagnostic, care and treatment options for affected children and their families.
For more information,visit the Walsh Laband read coverage on our science blog, Vector:
- Solving medical mysteries: The Undiagnosed Disease Network(polymicrogyria)
- Saving Grace: A ‘whodunit’ solved with clues from the Middle East(microcephaly)
Developmental Dysplasia of the Hip (DDH)
Investigators
Ingrid A. Holm, MD, MPH(首席研究员)
Louis M. Kunkel, PhD Young-Jo Kim, MD, PhD
Young-Jo Kim, MD, PhD
Developmental dysplasia of the hip (DDH),通常被称为先天性髋关节脱位,是一个有限公司mmon disease of early childhood. Its incidence is thought to vary from 1 to 4 per 1,000 births, although an incidence of up to 13 per 1,000 births has been reported. DDH has a strong genetic component, with a polygenic (multiple-gene) component thought to be responsible for acetabular dysplasia, and a single-gene component for the lax joint capsule. Evidence suggests a relatively high rate of generalized joint laxity (GJL) in patients with DDH associated with defects in collagen.
We hypothesize that the association between DDH and collagen genes is strongest in children with GJL, and that we will be able to identify genes associated with DDH in these children. We also hypothesize that patients with GJL inherit DDH in a pattern that is close to Mendelian, whereas those without GJL will show a multifactorial inheritance pattern. We are using transmission disequilibrium testing (TDT) to test the association between DDH and candidate collagen genes and explore the mode of inheritance of DDH in both patients with and without GJL. We will also compare the degree of association of DDH with the candidate genes.
Interstitial Cystitis/Painful Bladder Syndrome
Investigators
Louis M. Kunkel, PhD(首席研究员)
Ingrid A. Holm, MD, MPH
Interstitial cystitis (IC) is a chronic, debilitating syndrome causing urinary urgency, urinary frequency, and/or pelvic pain in the absence of any known cause. Although epithelial dysfunction, abnormal mast cell activity, and nerve damage have all been implicated in IC, the importance of each of these factors is still unclear.
Our preliminary data, from endogamous families in Bulgaria (meaning those that tend to marry within a specific ethnic/social group), indicate that there is linkage between IC and DNA polymorphic markers. By examining the extent of DNA shared on disease chromosomes in this unique cohort, we can identify a set of mutations that will provide tools for the effective diagnosis and treatment of IC.
The aims of this study are to: 1) collect DNA samples and medical/family history data from multigenerational families from the United States and Bulgaria; 2) perform high-density linkage analysis in the most informative pedigrees to establish genetic linkage between IC and DNA polymorphic markers; and 3) identify and verify any positional candidate genes by direct sequencing.
Visit the Kunkel Lab for more information.
Muscular Dystrophy
The muscular dystrophies are a group of diseases that can begin early or later in life, and can be relatively mild, moderate or severe. Severe cases may lead to death in early infancy, and even milder cases can cause significant life-long muscle weakness. Muscular dystrophies are inherited in different ways, including both X-linked and autosomal inheritance.
Since the dystrophin gene was cloned,muscular dystrophy research has significantly progressed. The functions of dystrophin and its associated protein complex (DAPC) are being elucidated. New advances have created the potential for several therapies, and our research is exploring these further with the goal of improving patients’ health and quality of life. For more information,visit Dr. Kunkel’s Neuromuscular Disorders Lab.