Engaging Indigenous Communities in Biomedical Research” - Chinese University … ·...

MALAYSIA

"GenEthics : Engaging Indigenous Communities in Biomedical Research”

APBEN Meeting, 29-30 Mar 2019, Hong Kong SAR

[email protected]

Monash University Sunway campus is jointly owned by Monash University and the Jeffrey Cheah Foundation

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Population engagement & fieldwork

GWAS, mtDNA, WGS,etc

HPC, BioIT analyses

New knowledge of genomic history,migration, selection, evolution


GenEthics (Oxford Dictionary)

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The ethics of, or ethical issues raised by (human population) genetics, genetic engineering, and biotechnology


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Impetus for doing what we do

Large global studies are continuing to miss a vast portion of the world’s genetic variation.

African, Latin American, Hispanics and Indigenous Peoples represent less than 4% of all samples analyzed.

These most vulnerable and traditionally underserved populationsare often subjected to Parachute Research

The importance of studying underrepresented populations to ensure that benefits of research are distributed fairly and to maximize potential for discovery

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How do I/we do ‘the right thing’?

There are as numerous Ethical Theories as there are theorists, philosophers and the time we can spend pondering…

In Practice, one has to consider/confront issues :

- Context

- Beliefs

- Culture

- Socio-Economics

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Quotes from the Indigenous Peoples

Although we are in different boats you in your boat and we in our canoe we share the same river of life . Chief Oren Lyons, Onandaga Nation

We are not myths of the past, ruins in the jungle, or zoos. We are people and we want to be respected, not to be victims of intolerance and racism. Rigoberta Menchu Tum

Ama Sua, Ama Kjella, Ama Lllulla! - Don't lie, don't cheat, don't be lazy". Quechua greeting during Inca times

http://www.betterworld.net/quotes/indigenous-quotes-2.htm

http://www.betterworld.net/movement/paths/indigenous.htm#heropix


Population genetics does not begin in labs, so where does it begin ?

Engaging individuals

Communities

Relevant agencies

So how does it begin ?

With R E S P E C T

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The ‘Orang Asli’ (Orang Asal)

Malay language meaning ‘Original Peoples’ – Indigenous to Peninsular Malaysia & descendants of the earliest migrants into South East Asia

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SenoiN =82,000

Mah Meri

Temiar

Semai

Jah Hut

Che Wong

Semoq Beri

Proto MalayN = 62,000

Orang Seletar

Semelai

Temuan

Jakun

Orang Kanaq

Orang Kuala

Source: JKOA (2008)

NegritoN = 4000

Jahai

Bateq

Kensiu

Lanoh

Mendriq

Kintak

The Orang Asli of Peninsula Malaysia<0.05% of national population

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Negrito

The Negrito•Austro-Asiatic speakers•Hunter-Gatherer•Sub-tribes /Location : Jehai (Belum), Bateq (Gua Musang), and Mendriq (Gua Musang)

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NegritoSenoiProto-Malays

Source: JHEOA (2008)

The Senoi

•Austro-Asiatic

•Slash & Burn farmers, Wood carvers

•Sub-tribes/Location: MahMeri (Carey

Island), Che Wong, and Semai (Cameron

Highlands)

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Source: JHEOA (2008)MEP2019

Proto-Malay

•Austronesian

•Seafarer & Farmer

•Sub-tribes/Locations: Orang Seletar

(Johor, Near Singapore), Jakun (Tasik

Chini), Temuan (Jelebu)


Population Genomics and Health of Orang AsliCommunities

Genome wide association studies (GWAS)

SNPs (Affy 50 K, Illumina Omni 2.5)

MtDNA and Whole Genome Sequencing (WGS)

3 projects

1. Hugo PanAsia consortium (2009) Mapping Human Genomic Diversity in Asia. Science 326, 1541.

2. Jinam et al. (2012) Evolutionary History of Continental Southeast Asians: Early Train Hypothesis based on genetic analyses of mt and autosomal DNA data. Mol.Biol Evol 29, 11, 3513.

3. Aghakhanian et al (2018). Metabolic Syndrome and Cardiometabolic Risk Factors among Indigenous Malaysians. Special Issue Indigenous Health, Public Health (in press)

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Investigation of 1928 individuals representing 73 Asian populations + 2 non Asian HapMap populations

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With the exception of India, all Asian populations form a monophyletic clade.

This suggests a single entry of modern humansinto Southeast and East Asia

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•Analysis of maternal mtDNA seqand SNP data from South East Asians

- mtDNA lineages indicate major migration events and timeframes

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Maximum-likelihood tree of mtDNA lineages

• Molecular clock calibrated using substitution rate 1.37 x 10-8 substitution per site per year for coding-region sequences

• Divergence between L (African) and M & N lineages is 160,000 YBP

• Coalescence time of: - All M lineages: 53,000 YBP & All N lineages: 55,000 YBP

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MALAYSIA

mtDNA macrohaplogroup frequenciesJehai

Temuan

Seletar

Bidayuh

F1a’c (30%)

N9a6a (35%)

N9a6 (71%)

E1b (19%)N21,N22

(39%)

M21a (28%)

M21a (38%)

R21 (25%)

Haplogroups which are representative of Austronesian expansion account for

less than 10% of haplogroup diversity in Austronesian groups from Malaysia

The three Austronesian groups (Bidayuh, Selatar, and Temuan) showed high frequencies of mtDNA

haplogroups, which originated from the Asian mainland ∼30,000–10,000 YBP, but low frequencies of

“Out of Taiwan” markers


Simplified tree of

mtDNA lineages

(haplogroups)

Image sauce: http://mitomap.org/MITOMAPMEP2019


PCA based on mtDNA haplogroup frequencies

Negrito

Island Southeast Asia

Continental Southeast Asia

Seletar

Bidayuh Temuan

Jehai

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Phylogeny & ages estimates of haplogroup N lineages

Haplogroups with mainland origin & TMRCA between 30,000-10,000 YBP: N21, N9a6,

N22, B5b2, B4b1a2, B4c2, B6, F1a1a, F1a’cHaplogroups which have mainland/continental origins with ages 30-10kya account

for the majority of haplogroup diversity in Austronesian groups from Malaysia

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Plausible migrations into Southeast Asia

1

43

2

Present

>60,000 YBP

30,000 YBP

10,000 YBP

2000 YBP

1

2

3

4

Early train?

Express train (OoT)

Early train?

Express train

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Out of Africa


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K Claw et al, Nature Communications, 9, 2957 (2018)


1. Understand tribal sovereignty and research regulation Research oversight structures and regulations are important to consider in Indigenous communities.

2. Engage and collaborate with the tribal community Involve the community in all aspects of the research process from the initial research engagement to the final dissemination of results

3. Build cultural competency Listen and learn from the community about their cultural perspectives

4. Improve transparency of research practices Make research goals and processes clear and understandable through frequent communication.

5. Build tribal research capacity Train and support community members in the research process.

6. Disseminate findings in a community-accessible format Collaborate with community partners to use culturally appropriate methods of disseminating and applying the findings.

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Alignment with UN-SDG 2030

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Terima Kasih Orang Asli communities, JKOA Malaysia, MOSTI, Malaysia, Monash University

My HDR students and Intl collaborators – TF. Aghakhanian, Jinam, S Naruya, M Stoneking, Eske Willerslev and team, OGVP consortium, HUGO Pan Asia consortium

Cardio-Metabolic & Indigenous Health Cluster –K Kadir, A. Zaini, S Harnida, YC Man, B Ahmad, I Othman, J Edo, M Ameen, BP Hoh, S. Harnida, CY Chui, et al

ICHG2016Phipps

Engaging Indigenous Communities in Biomedical Research” - Chinese University … ·...

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