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3s1: Evolution of health and disease > Papers > Flashcards

Papers Flashcards

1
Q

What study is an overview of MS and hygiene hypothesis?

A

7-year study of patients with multiple sclerosis, some of whom had worm infections while others did not

Patients without worms rapidly worsened; those with worms did not

5 years in patient suffered from worm infection so had anti-helminths and MS symptoms returned

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2
Q

How did they treat MS using worms?

A

Phase 1 clinical trial using eggs of pig whipworms, Trichuris suis, chosen because they elicit immune responses in the human gut without establishing a damaging infection

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3
Q

What were the results of the pig whipworm immune response?

A

The patients either improved or did not get worse during worm therapy.
That cleared the way for larger phase 2 and phase 3 trials that could lead to FDA approval of worm therapy in the USA

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4
Q

How does the menstrual cycle increase risk breast cancer?

A

Each menstrual cycle, breast tissue differentiates and multiplies, then regresses, and each such episode involves cell divisions with mitoses that allow somatic mutations

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5
Q

What is the difference in number of menstrual cycles in modern vs naturally reproducing women?

A

Modern - ~350 mentrual cycles per lifetime
Natural - ~70 mentrual cycles per lifetime

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6
Q

What is the difference between natural and modern reproduction?

A

Naturally reproducing population without contraception, a woman has several children, breast feeds them and experiences lactational amenorrhoea while breast feeding

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7
Q

What is the trade off with modern contraception?

A

Contraception is, however, protective against ovarian cancer

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8
Q

What are the two hypothesis of the menopause evolutution?

A

Mother
Grandmother

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9
Q

What is the mother hypothesis?

A

IF the probability of the mother dying in childbirth, or of the child dying in infancy, rises sufficiently with age, then there will come a point where selection will favour mothers who stop reproducing to ensure survival of their last child

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10
Q

What is the grandmother hypothesis?

A

Menopause evolved to free grandmothers from rearing their own infants so that they could help their daughters rear grandchildren

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11
Q

What is host tolerance?

A

Host should choose to tolerate rather than resist an invading pathogen is that the costs of defence can exceed the benefits

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12
Q

What is an example of host tolerance?

A

1918 influenza pandemic, where mortality rates were especially high among young adults with healthy immune systems capable of mounting a vigorous response

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13
Q

What happens with young adults with spanish flu?

A

The viral infection induced a cytokine storm that provoked intense inflammation, causing lungs to fill with fluid and enabling secondary bacterial infections that in many cases led to death from pneumonia

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14
Q

What are the impacts of chronic inflammation induced by infections?

A

20 per cent of adult cancer

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15
Q

What is the impact on anti-inflammatory agents on diseases?

A

Anti-inflammatory agents, including aspirin and statins, significantly reduce the risk of heart attack and stroke

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16
Q

What is an overview of phage therapy?

A

Killing pathogenic bacteria within the human host with viruses that evolved to infect bacteria, not humans

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17
Q

What are the advantages of using phages?

A

Phage have the advantages that they multiply, increasing the dose, in proportion to the number of bacteria available and they co-evolve with their bacterial hosts

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18
Q

What is the current outlook on phage therapy?

A

Poland and Russia, where more than 1000 patients have been treated
Increased focus in the west due to rapid rise of antibiotics

19
Q

What is the aim of targetting of production of bacterial signals?

A

The production of the signals is costly, and the introduction into the population of mutants that cheated by not producing the signals might so disrupt coordination that infection became inefficient or was even blocked entirely

20
Q

What can be the problem with imperfect vaccine?

A

Human intervention into the lives of pathogens with the greatest identified potential to make pathogens much more lethal than they already are

21
Q

Has imperfect vaccine led to increased lethality?

A

Only been experimentally confirmed in mice and chickens

22
Q

What is an overview of the cancer deaths amogst mammals?

A

Cancer accounts for 46 per cent of deaths in wild mice kept in the laboratory
25 per cent of human deaths in the USA
20 per cent of dog deaths
18 per cent of beluga deaths

23
Q

What is an overview of cancer deaths within dogs?

A

Osteosarcomas occur 200 times more frequently in large breeds of dogs than in small or medium-sized breeds

24
Q

What is an example of evolution in Inuit’s?

A

Two variants in the fatty acid desaturase enzymes (FADS) region

25
Q

Why did the FADS varients evolve?

A

Arctic environment and a marine diet rich in omega-3 polyunsaturated fatty (FADS), which are important modulators of fatty acid composition

26
Q

What are the tradeoffs for FADS in Inuit population?

A

Two variants in the FADS region were significantly associated with short stature in the Inuits, possibly because of the influence of fatty acid composition on growth hormone regulation

27
Q

What are the tradeoffs in FADS in european populations?

A

These variants were also associated with height in a larger study of Europeans, but the variants were present at low frequencies

28
Q

What are pygmy populations?

A

(commonly referred to as a “pygmy” phenotype), which is defined as an average height of <150 cm in adult males

29
Q

Where are pygmy populations found?

A

Short stature trait is an example of convergent evolution in rainforest hunter-gatherer (RFHG) populations

30
Q

What tests were used for examining pygmy populations?

A

locus-specific branch length (LSBL) and XP-EHH tests

31
Q

What did the genetic tests on pygmy populations show?

A

15-Mb region on chromosome 3 that shows signatures of strong positive selection

32
Q

What traits were shown with evolution in african pygmies?

A

Pygmies, including DOCK3, which is associated with height variation in non-Africans, and CISH

33
Q

What is an overview of CISH?

A

Important in immune response but also inhibits human growth hormone receptor activity, indicating that short stature could be a product of selection acting on pleiotropic loci

34
Q

What is an overview of the evolutionairy histroy of pygmy trait?

A

RFHG and neighboring agriculturalist populations in Uganda exhibit a distinct set of loci associated with short stature, which raises the possibility of convergent evolution of this trait across the RFHGs in Africa

35
Q

What are the problems with living with Tibetian Plateau?

A

Insufficient supply of oxygen to vital organs (hypoxia)

36
Q

What were the genome studies of Andean, Ethiopian and Tibetian genomes?

A

Signatures of positive selection were found repeatedly at genes involved in the hypoxia-inducible factor (HIF) pathway

37
Q

What is the haplotype background of different hypoxia genomes?

A

Different haplotype backgrounds (for example, EGLN1 in Andean and Tibetan populations) owing to convergent evolution

38
Q

What is tibetian population gene selected upon?

A

One of the strongest signals of selection in the Tibetan populations is at EPAS1, a transcription factor influencing the HIF pathway

39
Q

What is the origin of EPAS1 gene?

A

Tibetan haplotype may have originated from introgression of genomic DNA from Denisovans

40
Q

What is an overview of modern Somoa weight?

A

Over 80% of Samoans are overweight or obese [body mass index (BMI) > 26 kg/m2], which is among the highest prevalence in the world

41
Q

What gene caused the high prevalence of obesity in the samoans?

A

Genotyping ~3000 Samoans, a missense variant in CREBRF was found to be associated with BMI and fasting glucose levels

42
Q

Why did the varient CREBRF gene evolve?

A

Variant is under strong recent positive selection, as evidenced by extended haplotype homozygosity and high allele frequency
The Samoan variant decreases energy use and increases adipose fat storage, suggesting that this variant may have been adaptive in the past by increasing tolerance to periods of starvation

43
Q

What are the cons of the CREBRF varient?

A

Associated with risk for obesity and type 2 diabetes in modern populations

3s1: Evolution of health and disease (10 decks)

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