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Extramural Papers of the Month

By Jerry Phelps
January 2010

Researchers Map the First Human Epigenome

A comparison of the epigenomes of embryonic stem cells and fibroblasts shows a pattern of methylation unique to stem cells according to a study supported by NIEHS. The novel methylation pattern may help to explain how stem cells maintain their pluripotent state.

The research team developed a high-throughput method to determine the methylation status of every cytosine molecule in the genome and to layer the resulting epigenomic map onto the genome it regulates. The technique was then applied human fibroblasts and human embryonic stem cells to determine if the epigenomes differed between differentiated cells that perform a specific job and cells that have the potential to become any cell type. The results showed that the fibroblasts had a high degree of expected CG-methylation, but the stem cells showed a surprising result. Their methylation pattern exhibited non-CG methylation, which previously had been considered a laboratory artifact.

To confirm the results, the experiments were repeated in a second embryonic stem cell line and in fibroblasts reprogrammed into induced pluripotent stem cells. Both of these cell-types exhibited the same high level of non-CG methylation.

This study provides the first complete high-resolution map of an epigenome superimposed on the human genome. This knowledge could be extremely valuable for understanding and developing treatments for diseases.

Citation: Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, et al.( Exit NIEHS 2009. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462(7271):315-322.

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Metal and Diesel Exhaust Linked to Respiratory Symptoms in Children

Perinatal exposure to metals from heating oil combustion and diesel exhaust particles in ambient air is associated with respiratory disorders in young inner city children, according to an NIEHS-funded study. The study is among the first to link metal exposure with respiratory symptoms in young children.

The study was conducted with children living in the South Bronx and Northern Manhattan. Pollutant levels and the presence of respiratory symptoms were compared. The research team found that exposures to the metals vanadium and nickel are risk factors for wheezing in young children. Residential oil combustion for heating is a major source of these metals. Elemental carbon, which is an indicator of exposure to diesel exhaust, was found to be linked to increased coughing, but only during the traditional cold and flu season, defined as September through April.

The findings increase the understanding of the effects of specific pollutants on the respiratory health of young children. The results are of special concern because the levels of nickel found in the air in the study areas are among the highest in the U.S., as are the rates of pediatric asthma. The children in this study will be followed to see if these effects persist and are associated with increased rates of respiratory diseases at later ages.

Citation: Patel MM, Hoepner L, Garfinkel R, Chillrud S, Reyes A, Quinn JW, et al.( Exit NIEHS 2009. Ambient metals, elemental carbon, and wheeze and cough in New York City children through 24 months of age. Am J Respir Crit Care Med 180(11):1107-1113.

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Spatial Epidemiology of Abused Drugs

Using wastewater samples from urban and rural areas in Oregon, researchers discovered patterns of illicit drug use that mimic those found in human epidemiologic studies. This study demonstrates the utility of wastewater-derived measurements of community drug-use and the potential for such measurements to more accurately represent the levels and distribution of drug abuse.

The research was co-funded by the National Institute on Drug Abuse and an NIEHS center grant to Oregon State University.

The researchers used single day samples from 96 municipalities representing 65 percent of the population of Oregon. The samples were analyzed for methamphetamine, 3,4 methylenedioxymethamphetamine (MDMA), and a metabolite of cocaine. The wastewater-derived drug load was consistent with expected drug-use patterns.

The cocaine metabolite was significantly higher in urban areas and below detection in many rural areas, whereas methamphetamine was found in all areas with no differences between urban and rural samples. MDMA was found in measurable levels in less than half of the municipalities, with higher amounts in urban areas.

Citation: Banta-Green CJ, Field JA, Chiaia AC, Sudakin DL, Power L, de Montigny L( Exit NIEHS. 2009. The spatial epidemiology of cocaine, methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) use: a demonstration using a population measure of community drug load derived from municipal wastewater. Addiction 104(11):1874-1880.

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Traffic and Childhood Asthma

A study conducted by NIEHS grantees at the University of Southern California estimates that nine percent of all childhood asthma cases in Long Beach and six percent in Riverside are attributable to traffic proximity. The study also found that ship emissions from the Los Angeles-Long Beach port complex contributed greatly to asthma exacerbations. The researchers estimated that 21 percent of yearly asthma-related bronchitis is caused by elevated nitrogen dioxide levels from ships.

Although there is an extensive body of research on the effects of traffic proximity on asthma risk, this study is one of a few that estimated the number of cases, the so-called burden of disease, associated with traffic in specific high risk communities. The researchers conclude that the traditional methods of estimating the burden of air pollution-related diseases highly underestimated the true effect. The results show that more than 2,200 cases of childhood asthma in Long Beach and Riverside are linked to living within 75 meters of a major road or highway. In addition, the severity of the asthma is greater, resulting in more frequent visits to a clinic or emergency room.

Unlike regional air pollutants, local traffic-related pollutants are not currently regulated. The authors conclude that traffic-related health effects should have a central role in planning, positioning, and expansion of transportation corridors.

Citation: Perez L, K├╝nzli N, Avol E, Hricko AM, Lurmann F, Nicholas E, et al.( Exit NIEHS 2009. Global goods movement and the local burden of childhood asthma in southern California. Am J Public Health 99 Suppl 3:S622-628.

(Jerry Phelps is a program analyst in the NIEHS Division of Extramural Research and Training. Each month, he contributes summaries of extramural papers to the Environmental Factor.)

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