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1.
Aust N Z J Public Health ; 48(2): 100143, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38626567

ABSTRACT

OBJECTIVE: This study aims to: 1) explore how alcohol and alcohol harm are framed in New Zealand national policy, strategy, and action plan documents; and 2) examine how these documents align with the WHO SAFER framework. METHODS: Keyword searches across government websites and Google were conducted in January 2021. Inclusion and exclusion criteria were applied to all identified documents, resulting in 22 being included for analysis in this study. An inductive and deductive thematic analysis of those documents was performed. RESULTS: Our inductive thematic analysis identified three themes, of which one is detailed in this study: 'Location of responsibility for addressing alcohol harms' with a focus on individuals and non-specific government agencies. Thematic results from the deductive analysis found that the most consistently referenced SAFER policies included brief interventions (68% of documents), followed by drink driving measures (45%), alcohol marketing (36%), alcohol availability (27%), and alcohol price (23%). The conversion rate from a document mentioning a SAFER framework policy area to making specific policy recommendations was usually less than or around 50%. CONCLUSIONS: The lack of alignment between New Zealand alcohol policy and the SAFER framework can be partially attributable to the absence of an updated national alcohol strategy (NAS). An updated NAS should identify responsible agencies, create a systematic monitoring and evaluation mechanism, and be consistent with the WHO SAFER framework. IMPLICATIONS FOR PUBLIC HEALTH: The analysis supports the need to update a national alcohol strategy to guide alcohol policy development.


Subject(s)
Alcohol Drinking , Health Policy , Public Policy , Humans , New Zealand , Alcohol Drinking/prevention & control , Alcohol Drinking/adverse effects , Alcoholic Beverages , Harm Reduction
2.
Addiction ; 119(1): 125-136, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37649140

ABSTRACT

AIMS: To estimate the health impacts of key modelled alcohol interventions among Maori (indigenous peoples) and non-Maori in New Zealand (NZ). DESIGN: Multi-stage life-table intervention modelling study. We modelled two scenarios: (1) business-as-usual (BAU); and (2) an intervention package scenario that included a 50% alcohol tax increase, outlet density reduction from 63 to five outlets per 100 000 people, outlet hours reduction from 112 to 50 per week and a complete ban on all forms of alcohol marketing. SETTING AND PARTICIPANTS: The model's population replicates the 2018 NZ population by ethnicity (Maori/non-Maori), age and sex. MEASUREMENTS: Alcohol consumption was estimated using nationally representative survey data combined with sales data and corrected for tourist and unrecorded consumption. Disease incidence, prevalence and mortality were calculated using Ministry of Health data. We used dose-response relationships between alcohol and illness from the 2016 Global Burden of Disease study and calculated disability rates for each illness. Changes in consumption were based on the following effect sizes: total intervention package [-30.3%, standard deviation (SD) = 0.02); tax (-7.60%, SD = 0.01); outlet density (-8.64%, SD = 0.01); outlet hours (-9.24%, SD = 0.01); and marketing (-8.98%, SD = 0.02). We measured health gain using health-adjusted life years (HALYs) and life expectancy. FINDINGS: Compared with the BAU scenario, the total alcohol intervention package resulted in 726 000 [95% uncertainty interval (UI) = 492 000-913 000] HALYs gained during the life-time of the modelled population. Maori experienced greater HALY gains compared with non-Maori (0.21, 95% UI = 0.14-0.26 and 0.16, 95% UI = 0.11-0.20, respectively). When modelled individually, each alcohol intervention within the intervention package produced similar health gains (~200 000 HALYs per intervention) owing to the similar effect sizes. CONCLUSIONS: Modelled interventions for increased alcohol tax, reduced availability of alcohol and a ban on alcohol marketing among Maori and non-Maori in New Zealand (NZ) suggest substantial population-wide health gains and reduced health inequities between Maori and non-Maori.


Subject(s)
Alcohol Drinking , Life Expectancy , Maori People , Humans , Morbidity , New Zealand/epidemiology , Prevalence , Alcohol Drinking/prevention & control , Mortality
3.
N Z Med J ; 136(1580): 40-47, 2023 Aug 04.
Article in English | MEDLINE | ID: mdl-37536310

ABSTRACT

AIMS: Over recent decades, a body of research has established the presence of pervasive health inequities experienced by Maori. Work to identify the root causes of inequities has focused on the unequal distribution of the determinants of good health, access to healthcare, and racism. This study contributes to a small but growing field of work which engages with Te Tiriti o Waitangi to critique key health documents, focusing on district health boards' (DHBs) annual plans. METHODS: A qualitative, directed content analytical approach was used to investigate whether DHBs' 2019/2020 annual plans were consistent with the principles of Te Tiriti o Waitangi, as identified by the Wai 2575 Waitangi Tribunal inquiry. RESULTS: While annual plans contained actions that aligned with the principles of active protection and equity, comparatively few related to the principles of options, partnership, and tino rangatiratanga. Overall, DHB actions operated to constrain options available to Maori and efforts to exercise the Tiriti-guaranteed right of tino rangatiratanga in the provision of health services. CONCLUSION: While DHBs' annual plans expressed commitment to Te Tiriti o Waitangi, their content did not give effect to these commitments. Significant shifts are necessary if future New Zealand Health Plans are Tiriti-responsive documents that deliver Tiriti-responsive health services.


Subject(s)
Health Inequities , Maori People , Racism , Humans , New Zealand
4.
J Paediatr Child Health ; 58(11): 1924-1928, 2022 11.
Article in English | MEDLINE | ID: mdl-35822942

ABSTRACT

On-going inequities in rates of fatal and non-fatal injury between tamariki Maori (Indigenous children) and non-Maori children in Aotearoa (New Zealand) are unacceptable and highlight breaches by the Crown in their obligations to Maori, outlined in Te Tiriti o Waitangi (The Treaty of Waitangi). Safekids Aotearoa, a national organisation tasked with reducing unintentional injuries to children (0-14 years), is shifting the focus of its programmes and resources to better align with Te Tiriti o Waitangi and to honour Maori knowledge, ideas and principles to eliminate inequity and support the pursuit of Pae Ora: Maori health aspirations for flourishing whanau (families) and tamariki. We provide an overview of Te Tiriti o Waitangi and its relevance to child injury prevention and the Te Tiriti-led response by Safekids Aotearoa, particularly around approaches to developing values and strengths-based safety messages. In doing so, we challenge and counter pervasive barriers to achieving equity and Pae Ora and describe how identifying and incorporating shared Maori values in a Te Tiriti-led agenda supports the work, ethos, programmes and relationships of Safekids Aotearoa in its journey toward equitable outcomes and Pae Ora for all. We highlight the importance of embedding prevention efforts and advocacy within a holistic framework of tamariki and whanau well-being embracing capability and strengths-based approaches.


Subject(s)
Native Hawaiian or Other Pacific Islander , Population Groups , Child , Humans , New Zealand
5.
N Z Med J ; 134(1543): 123-132, 2021 10 08.
Article in English | MEDLINE | ID: mdl-34695083

ABSTRACT

Enduring health inequities exist between Maori and non-Maori children within child injury prevention in Aotearoa. These inequities reflect broader patterns of health inequity experienced by Indigenous peoples globally and in Aotearoa. We assert their existence is the result of the ongoing impacts of colonisation and the dominant Pakeha framing by which injury prevention messages and interventions in Aotearoa have largely been developed. We argue the need for a strengths-based approach, grounded in matauranga Maori (traditional Maori knowledge) and te ao Maori (traditional Maori worldview) perspectives, to form the basis of more effective child injury prevention messaging and interventions. In this viewpoint, we detail foundational elements of matauranga Maori, tikanga (customs), kawa (practices) and matapono (values) that underlie Maori culture and contain protective elements and safety principles that can be readily applied to injury prevention messaging. We present two values-based child-rearing practices: (1) tuakana (older sibling/s) and teina (younger sibling/s) relationships and (2) kotahitanga (collective), which are determined by matapono that illustrate the value of a Maori framework. Incorporating a kaupapa Maori (Maori perspective/s) approach to injury prevention is necessary to reduce health inequities between Maori and non-Maori. Moreover, it offers a culturally safe approach that is responsive to Maori and enables tamariki (children) and whanau (families) to flourish.


Subject(s)
Child Rearing/ethnology , Medicine, Traditional/methods , Native Hawaiian or Other Pacific Islander , Peer Group , Wounds and Injuries/prevention & control , Child , Health Equity , Humans , Indigenous Peoples , New Zealand
6.
Front Med Technol ; 3: 729658, 2021.
Article in English | MEDLINE | ID: mdl-35047956

ABSTRACT

Objectives: The provision of high-quality personal protective equipment (PPE) has been a critical challenge during the COVID-19 pandemic. We evaluated an alternative strategy, mass deployment of a powered air-purifying respirator (PeRSo), in a large university hospital. Methods: We performed prospective user feedback via questionnaires sent to healthcare workers (HCWs) issued PeRSos, economic analysis, and evaluated the real-world impact. Results: Where paired responses were available, PeRSo was preferred over droplet precautions for comfort, patient response, overall experience, and subjective feeling of safety. For all responses, more participants reported the overall experience being rated "Very good" more frequently for PeRSo. The primary limitation identified was impairment of hearing. Economic simulation exercises revealed that the adoption of PeRSo within ICU is associated with net cost savings in the majority of scenarios and savings increased progressively with greater ITU occupancy. In evaluation during the second UK wave, over 3,600 respirators were deployed, all requested by staff, which were associated with a low staff absence relative to most comparator hospitals. Conclusions: Health services should consider a widespread implementation of powered reusable respirators as a safe and sustainable solution for the protection of HCWs as SARS-CoV-2 becomes an endemic viral illness.

7.
Child Adolesc Psychiatr Clin N Am ; 28(3): 509-521, 2019 07.
Article in English | MEDLINE | ID: mdl-31076124

ABSTRACT

Lesbian, gay, bisexual, and transgender (LGBT) youth have unique risk factors that predispose them to depression at higher rates than their non-LGBT peers. Family rejection, bullying, and lack of societal acceptance can contribute to negative health outcomes. Additionally, youth with gender dysphoria may need or benefit from medical interventions. LGBT youth also have the same risk factors as non-LGBT youth, requiring clinicians to decipher risk factors associated with sexual and gender minority identity status, general risk factors, and relationships among them. Assessment of these risk factors and implementation of targeted interventions are important when treating depression in LGBT youth.


Subject(s)
Depression/psychology , Mental Health , Resilience, Psychological , Sexual and Gender Minorities/statistics & numerical data , Adolescent , Humans , Risk Factors , Sexual and Gender Minorities/psychology , Social Stigma , Suicide/trends
8.
Early Hum Dev ; 132: 45-51, 2019 05.
Article in English | MEDLINE | ID: mdl-30974313

ABSTRACT

BACKGROUND: Poor maternal health, disadvantageous exposures during pregnancy and unfavourable perinatal events are associated with adverse trajectories in offspring cognitive development. AIM: To examine longitudinal associations between antenatal maternal, perinatal and maternal health characteristics and children's early cognitive development across executive control, motor ability and receptive language domains. STUDY DESIGN, SUBJECTS AND OUTCOME MEASURES: Analyses comprised interview and observational data from 4587 children and their mothers enrolled in the longitudinal Growing Up in New Zealand cohort study. Children's executive control (Luria hand clap task), motor skills (mothers' report) and receptive language ability (Peabody Picture Vocabulary Test) were assessed at age 4.5 years. Multivariate logistic regression analyses were conducted, controlling for sociodemographic factors. RESULTS: Smoking pre- and during pregnancy, no folate intake during first trimester and low birth weight were risk factors for poorer executive control. Perceived stress during pregnancy, no folate intake during first trimester and low birth weight were all risk factors for poorer motor ability. Smoking pre-pregnancy, antenatal anxiety and no folate intake during first trimester were risk factors for poorer receptive language ability. CONCLUSION: Adverse ante- and perinatal environments are associated with poorer executive control, motor and receptive language abilities in early childhood. Improving maternal education and support especially for more disadvantaged mothers during pregnancy may reduce the potential deleterious impact of adverse ante- and perinatal conditions on children's early cognition.


Subject(s)
Child Development , Cognition , Folic Acid Deficiency/epidemiology , Prenatal Exposure Delayed Effects/epidemiology , Stress, Psychological/epidemiology , Tobacco Smoking/epidemiology , Adult , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Language , Male , Motor Skills , New Zealand , Pregnancy
9.
Int J Drug Policy ; 54: 123-129, 2018 04.
Article in English | MEDLINE | ID: mdl-29428887

ABSTRACT

BACKGROUND: The predominant framing of indigenous people's alcohol use as problematic has resulted in narrow understandings of indigenous alcohol use in general. In particular, there has been little exploration of how Maori, those indigenous to Aotearoa/New Zealand, contextualise and understand their alcohol use. To build on current understandings of Maori alcohol use, this study explored the broader and socially shared meanings of alcohol use from the perspectives of older Maori. METHODS: Hui (meeting/s) were held with five kaupapa whanau (groups with a common purpose) comprising older Maori (n = 19) who shared their perspectives on Maori alcohol use. Data were analysed using a master/counter discursive narrative analytical framework. RESULTS: The results show that older Maori drew on a number of discursive strategies to construct three cultural narratives of Maori alcohol use. These were: 'Not all Maori are problem drinkers', 'There is good Maori alcohol use', and 'Alcohol is not the problem'. These narratives simultaneously supported and challenged the dominant narrative that problematises Maori alcohol use. CONCLUSION: These findings can be used to inform future research to show Maori understandings of alcohol use. Such research will support the development of culturally responsive alcohol policy and health promotion initiatives aimed at addressing alcohol related issues among Maori and thereby improve Maori health and wellbeing.


Subject(s)
Alcohol Drinking/psychology , Health Knowledge, Attitudes, Practice , Native Hawaiian or Other Pacific Islander/psychology , Aged , Female , Focus Groups , Humans , Male , Middle Aged , New Zealand
10.
J Med Regul ; 102(2): 7-12, 2016.
Article in English | MEDLINE | ID: mdl-27754500

ABSTRACT

Conversion therapies are any treatments, including individual talk therapy, behavioral (e.g. aversive stimuli), group therapy or milieu (e.g. "retreats or inpatient treatments" relying on all of the above methods) treatments, which attempt to change an individual's sexual orientation from homosexual to heterosexual. However these practices have been repudiated by major mental health organizations because of increasing evidence that they are ineffective and may cause harm to patients and their families who fail to change. At present, California, New Jersey, Oregon, Illinois, Washington, DC, and the Canadian Province of Ontario have passed legislation banning conversion therapy for minors and an increasing number of US States are considering similar bans. In April 2015, the Obama administration also called for a ban on conversion therapies for minors. The growing trend toward banning conversion therapies creates challenges for licensing boards and ethics committees, most of which are unfamiliar with the issues raised by complaints against conversion therapists. This paper reviews the history of conversion therapy practices as well as clinical, ethical and research issues they raise. With this information, state licensing boards, ethics committees and other regulatory bodies will be better able to adjudicate complaints from members of the public who have been exposed to conversion therapies.

11.
J Ethn Subst Abuse ; 14(3): 251-69, 2015.
Article in English | MEDLINE | ID: mdl-26114657

ABSTRACT

This study investigated alcohol use, hazardous and binge drinking prevalence, and their relationships to socio-demographic variables in community dwelling older Maori adults in New Zealand. Alcohol use, hazardous drinking, and binge drinking were assessed with the AUDIT-C in a cross-sectional postal survey of 1042 older Maori people randomly selected from the New Zealand Electoral Roll. A total of 41.2% of all participants reported drinking at hazardous levels. Odds ratios from binomial logistic regression showed hazardous drinking was significantly more likely to occur among males, current smokers, and those with higher local self-contained network scores. Binge drinking was reported by 19.6% of the sample, with odds ratios indicating that males, current smokers, and those with higher Maori cultural identification scores were significantly more likely to report binge drinking. The high rates of hazardous and binge drinking prevalence reported in the current study raise issues of concern when considering the health of older Maori people. Results indicate that social networks, gender, smoking status, and Maori cultural identification may influence hazardous and binge drinking alcohol use. However, limitations of the present study also highlight the need for more focused and in-depth research to be conducted with older Maori people to understand the sociocultural context in which alcohol use occurs.


Subject(s)
Alcohol Drinking/ethnology , Alcohol-Related Disorders/ethnology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , New Zealand/ethnology
12.
Child Adolesc Ment Health ; 19(1): 69-73, 2014 Feb.
Article in English | MEDLINE | ID: mdl-32878366

ABSTRACT

BACKGROUND: We examined the experiences of incarcerated adolescent males (N = 29) who participated in a one-day meditation retreat and 10-week meditation programme. METHOD: Self-report surveys assessing mindfulness, self-regulation, impulsivity and stress; behavioural assessments; and focus group data were examined. RESULTS: We observed significantly higher scores in self-regulation (p = .012) and psychometric markers demonstrated psychological enhancement. No behavioural change was observed. Six themes emerged: enhanced well-being, increased self-discipline, increased social cohesiveness, expanded self-awareness, resistance to meditation and future meditation practice. CONCLUSIONS: Early evidence suggests that meditation training for incarcerated youth is a feasible and promising intervention.

13.
Toxicol Appl Pharmacol ; 271(3): 372-85, 2013 Sep 15.
Article in English | MEDLINE | ID: mdl-22142766

ABSTRACT

A critical challenge for environmental chemical risk assessment is the characterization and reduction of uncertainties introduced when extrapolating inferences from one species to another. The purpose of this article is to explore the challenges, opportunities, and research needs surrounding the issue of how genomics data and computational and systems level approaches can be applied to inform differences in response to environmental chemical exposure across species. We propose that the data, tools, and evolutionary framework of comparative genomics be adapted to inform interspecies differences in chemical mechanisms of action. We compare and contrast existing approaches, from disciplines as varied as evolutionary biology, systems biology, mathematics, and computer science, that can be used, modified, and combined in new ways to discover and characterize interspecies differences in chemical mechanism of action which, in turn, can be explored for application to risk assessment. We consider how genetic, protein, pathway, and network information can be interrogated from an evolutionary biology perspective to effectively characterize variations in biological processes of toxicological relevance among organisms. We conclude that comparative genomics approaches show promise for characterizing interspecies differences in mechanisms of action, and further, for improving our understanding of the uncertainties inherent in extrapolating inferences across species in both ecological and human health risk assessment. To achieve long-term relevance and consistent use in environmental chemical risk assessment, improved bioinformatics tools, computational methods robust to data gaps, and quantitative approaches for conducting extrapolations across species are critically needed. Specific areas ripe for research to address these needs are recommended.


Subject(s)
Environmental Pollutants/toxicity , Genomics/methods , Animals , Humans , Proto-Oncogene Mas , Risk Assessment/methods
14.
Child Adolesc Psychiatr Clin N Am ; 20(4): 681-8, 2011 Oct.
Article in English | MEDLINE | ID: mdl-22051005

ABSTRACT

This article focuses on considerations for natal females who present in the adolescent years with concerns related to their gender. They maybe individuals previously evaluated in their childhood years who have persisted with gender variance or gender identity disorder (GID) in DSM-IV, or they may be presenting for the first time in their adolescent years. The article discusses how to assess adolescents who come for evaluation and what treatments and other resources are available for them and their families. Where there seem to be differences between boys and girls with gender identity issues, they will be noted.


Subject(s)
Disorders of Sex Development , Gender Identity , Transsexualism , Adolescent , Disorders of Sex Development/diagnosis , Disorders of Sex Development/psychology , Disorders of Sex Development/therapy , Female , Humans , Transsexualism/diagnosis , Transsexualism/psychology , Transsexualism/therapy
15.
Dis Aquat Organ ; 96(2): 169-74, 2011 Sep 09.
Article in English | MEDLINE | ID: mdl-22013756

ABSTRACT

The dissemination of the virulent pathogen Batrachochytrium dendrobatidis (Bd) has contributed to the decline and extinction of many amphibian species worldwide. Several different strains have been identified, some of which are sympatric. Interactions between co-infecting strains of a pathogen can have significant influences on disease epidemiology and evolution; therefore the dynamics of multi-strain infections is an important area of research. We stained Bd cells with 2 fluorescent BODIPY fatty acid probes to determine whether these can potentially be used to distinguish and track Bd cell lines in multi-strain experiments. Bd cells in broth culture were stained with 5 concentrations of green-fluorescent BODIPY FL and red-fluorescent BODIPY 558/568 and visualised under an epifluorescent microscope for up to 16 d post-dye. Dyed strains were also assessed for growth inhibition. The most effective concentration for both dyes was 10 pM. This concentration of dye produced strong fluorescence for 12 to 16 d in Bd cultures held at 23 degrees C (3 to 4 generations), and did not inhibit Bd growth. Cells dyed with BODIPY FL and BODIPY 558/568 can be distinguished from each other on the basis of their fluorescence characteristics. Therefore, it is likely that this technique will be useful for research into multi-strain dynamics of Bd infections.


Subject(s)
Amphibians/microbiology , Chytridiomycota/isolation & purification , Fluorescent Dyes , Animals , Boron Compounds , Chytridiomycota/classification
16.
Dis Aquat Organ ; 92(2-3): 159-63, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21268977

ABSTRACT

The susceptibility of Archey's frog Leiopelma archeyi to Batrachochytrium dendrobatidis (Bd) is unknown, although one large population is thought to have declined sharply due to chytridiomycosis. As primary infection experiments were not permitted in this endangered New Zealand species, 6 wild-caught L. archeyi that naturally cleared infections with Bd while in captivity were exposed again to Bd to assess their immunity. These frogs were from an infected population at Whareorino, which has no known declines. All 6 L. archeyi became reinfected at low intensities, but rapidly self cured, most by 2 wk. Six Litoria ewingii were used as positive controls and developed heavier infections and clinical signs by 3 wk, demonstrating that the zoospore inoculum was virulent. Six negative controls of each species remained uninfected and healthy. Our results show that L. archeyi that have self cured have resistance to chytridiomycosis when exposed. The pattern is consistent with innate or acquired immunity to Bd, and immunological studies are needed to confirm this.


Subject(s)
Chytridiomycota/physiology , Mycoses/veterinary , Ranidae , Animals , Mycoses/immunology , Mycoses/microbiology
17.
BMC Genet ; 10: 81, 2009 Dec 09.
Article in English | MEDLINE | ID: mdl-20003225

ABSTRACT

BACKGROUND: To assess the utility of haplotype association mapping (HAM) as a quantitative trait locus (QTL) discovery tool, we conducted HAM analyses for red blood cell count (RBC) and high density lipoprotein cholesterol (HDL) in mice. We then experimentally tested each HAM QTL using published crosses or new F2 intercrosses guided by the haplotype at the HAM peaks. RESULTS: The HAM for RBC, using 33 classic inbred lines, revealed 8 QTLs; 2 of these were true positives as shown by published crosses. A HAM-guided (C57BL/6J x CBA/J)F2 intercross we carried out verified 2 more as true positives and 4 as false positives. The HAM for HDL, using 81 strains including recombinant inbred lines and chromosome substitution strains, detected 46 QTLs. Of these, 36 were true positives as shown by published crosses. A HAM-guided (C57BL/6J x A/J)F2 intercross that we carried out verified 2 more as true positives and 8 as false positives. By testing each HAM QTL for RBC and HDL, we demonstrated that 78% of the 54 HAM peaks were true positives and 22% were false positives. Interestingly, all false positives were in significant allelic association with one or more real QTL. CONCLUSION: Because type I errors (false positives) can be detected experimentally, we conclude that HAM is useful for QTL detection and narrowing. We advocate the powerful and economical combined approach demonstrated here: the use of HAM for QTL discovery, followed by mitigation of the false positive problem by testing the HAM-predicted QTLs with small HAM-guided experimental crosses.


Subject(s)
Cholesterol, HDL/blood , Cholesterol, HDL/genetics , Erythrocyte Count , Haplotypes , Mice, Inbred Strains/genetics , Quantitative Trait Loci , Alleles , Animals , Computational Biology , Female , Male , Mice
18.
Physiol Genomics ; 39(3): 172-82, 2009 Nov 06.
Article in English | MEDLINE | ID: mdl-19671657

ABSTRACT

Diets high in fat and cholesterol are associated with increased obesity and metabolic disease in mice and humans. To study the molecular basis of the metabolic response to dietary fat, 10 inbred strains of mice were fed atherogenic high-fat and control low-fat diets. Liver gene expression and whole animal phenotypes were measured and analyzed in both sexes. The effects of diet, strain, and sex on gene expression were determined irrespective of complex processes, such as feedback mechanisms, that could have mediated the genomic responses. Global gene expression analyses demonstrated that animals of the same strain and sex have similar transcriptional profiles on a low-fat diet, but strains may show considerable variability in response to high-fat diet. Functional profiling indicated that high-fat feeding induced genes in the immune response, indicating liver damage, and repressed cholesterol biosynthesis. The physiological significance of the transcriptional changes was confirmed by a correlation analysis of transcript levels with whole animal phenotypes. The results found here were used to confirm a previously identified quantitative trait locus on chromosome 17 identified in males fed a high-fat diet in two crosses, PERA x DBA/2 and PERA x I/Ln. The gene expression data and phenotype data have been made publicly available as an online tool for exploring the effects of atherogenic diet in inbred mouse strains (http://cgd-array.jax.org/DietStrainSurvey).


Subject(s)
Diet, Atherogenic , Gene Expression Profiling/methods , Liver/metabolism , Analysis of Variance , Animals , Cluster Analysis , Female , Male , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Inbred C57BL , Mice, Inbred DBA , Mice, Inbred Strains , Oligonucleotide Array Sequence Analysis , Species Specificity
19.
Genetics ; 180(4): 2227-35, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18845850

ABSTRACT

Dissecting the genes involved in complex traits can be confounded by multiple factors, including extensive epistatic interactions among genes, the involvement of epigenetic regulators, and the variable expressivity of traits. Although quantitative trait locus (QTL) analysis has been a powerful tool for localizing the chromosomal regions underlying complex traits, systematically identifying the causal genes remains challenging. Here, through its application to plasma levels of high-density lipoprotein cholesterol (HDL) in mice, we demonstrate a strategy for narrowing QTL that utilizes comparative genomics and bioinformatics techniques. We show how QTL detected in multiple crosses are subjected to both combined cross analysis and haplotype block analysis; how QTL from one species are mapped to the concordant regions in another species; and how genomewide scans associating haplotype groups with their phenotypes can be used to prioritize the narrowed regions. Then we illustrate how these individual methods for narrowing QTL can be systematically integrated for mouse chromosomes 12 and 15, resulting in a significantly reduced number of candidate genes, often from hundreds to <10. Finally, we give an example of how additional bioinformatics resources can be combined with experiments to determine the most likely quantitative trait genes.


Subject(s)
Computational Biology/methods , Quantitative Trait Loci , Animals , Crosses, Genetic , Databases, Genetic , Haplotypes , Lipoproteins, HDL/genetics , Mice
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