Recent Studies in The Genetics of Genetic Resistance to Parasite - - PowerPoint PPT Presentation

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Recent Studies in Genetic Resistance to Parasite Infection in Ruminants

• David Notter

Department of Animal & Poultry Sciences Virginia Tech

The Genetics of Parasite Resistance

• Worm resistance clearly has a

heritable genetic component

• Large differences in parasite

resistance exist among breeds

• But there are also clear and

substantial genetic differences within breeds

Opportunities to Enhance Parasite Resistance

• Parasite resistance is a quantitative

performance trait—no different from weaning weight or wool quality—and will respond to selection in any breed.

Opportunities to Enhance Parasite Resistance

• Innate levels of parasite resistance are

highest in Caribbean hair breeds such as the

• St. Croix and Barbados Blackbelly, African

breeds such as the Red Maasai and naturally selected wool breeds such as the Gulf Coast and Florida Natives

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Opportunities to Enhance Parasite Resistance

• The Katahdin breed was created by crossing

Caribbean hair breeds with temperate wool breeds in the USA and shares some of the genetically mediated resistance from its hair sheep ancestor.

Measuring parasite resistance

• Measures of parasite resistance

include: fecal egg counts, packed cell volume (hematocrit), FAMACHA

• Must measure resistance when worms

are present—cannot just set a calendar date

• Must coordinate measurements with

the deworming schedule and protocol

Understanding and Utilizing Parasite Resistance

• Document and utilize breed diversity
• Develop program for breed improvement

– Data collection—classic genetic evaluations – EBVs

• Functional genomic strategies—build

understanding

• Genome-wide screening and marker detection

– What animals, what populations?

Understanding and Utilizing Parasite Resistance

• With regard to parasite resistance, all hair

sheep are NOT created equal

• Breeds of Caribbean origin have generally

high levels of resistance

• Dorper is much less resistant, as expected

from its origins as an arid-lands breed.

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Mean Fecal Egg Counts Following Natural Infection of Wether Lambs

500 1000 1500 2000 2001 2002

Year Fecal egg count

Dorset cross Dorper cross Katahdin Hair sheep crosses

Mean Packed Cell Volume Following Natural Infection of Wether Lambs

20 22 24 26 28 30 32 34 36 2001 2002

Year PCV, %

Dorset cross Dorper cross Katahdin Hair sheep crosses

Measuring parasite resistance (fecal egg counts) in Katahdin

Spring-born lambs Monitor parasite levels (FAMACHA) Maintain normal parasite mgmt. (FAMACHA, etc) Collect a fecal sample 4 to 5 wk after deworming (Acquired resistance) Collect fecal samples at first deworming (Innate resistance) If >10-20% dewormed, then deworm ALL lambs. Otherwise (we will) exclude recently dewormed lambs from the data (Optional for Katahdin)

Katahdin 2003-05 Fecal Egg Count EPD Study

• Six flocks; each with at least 2 sires

and a minimum of 10-12 lambs per sire

• 850 lambs by 26 sires over 3 years
• Average ages of ~8 and ~22 weeks
• Heritabilities for FEC

– 0.48 at 8 wks – 0.54 at 22 weeks – genetic correlation of 0.50.

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Heritabilities from Ohio Parasite Project

• 10 Flocks
• Measure lambs at approximately 8 wk (n =

244), 13 wk (n = 289), and 17 wk (n = 139)

8 wk 13 wk 17 wk Mean FEC 8 wk 0.41 568 epg 13 wk 0.52 1,486 epg 17 wk 0.54 1,061 epg

Katahdin 2006-07 Fecal Egg Count EPD Study

• Three measurement times:

– Early-season FEC (innate resistance) at 35 to 92 days. – Mid-season FEC shortly after weaning at 65 to 127 days. – Late-season FEC at 92 to 184 days.

• Only groups with Mean FEC > 500 epg

Heritability and Litter (maternal) variance components for High FEC Contemporary Groups

High FEC Data Early Mid- Late Heritability 0.27 0.65 0.51 Litter (Maternal) 0.34 0.11 0.29

Correlations among FEC at different ages

High FEC Data Early- Mid Early- Late Mid- Late Genetic 0.85 0.76 0.99 Phenotypic 0.55 0.38 0.95

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Average PFEC EBVs by sires--sires with at least 10 and minimum accuracy of 0.75 for WFEC or PFEC EBVs (N = 127)

• 200
• 150
• 100
• 50

50 100 150 200 250 300 350 400 450 500 Sires Average PFEC EBV, %

Rapid Genetic Improvement Is Possible for Fecal Egg Counts

• Heritabilities are relatively high at 25% and

appear to be very high (near 50%) in Katahdin

• Very high levels of variation for FEC
• Animals can be successfully evaluated early

in life

• In pedigree flocks with EPDs, progeny

testing can occur along with the individual evaluations

Predicted genetic change (in %) over 20 years with single-trait selection for:

Functional Genomics

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Hair Sheep N=24 Wool Sheep N=24 Total of 48 Jan./Feb. ’07 spring-born lambs

• Lambs were primed with 2,000 H.

contortus L3 larvae for 4 weeks prior to infection.

• Dewormed
• Final infection of 10,000 L3 H.

contortus larvae

• Divided into 3 blocks

3 5 7 7 5 3

Days post infection Days post infection 7 6 5 4 3 2 1 0 Block A 7 6 5 4 3 2 1 0 Block B 7 6 5 4 3 2 1 0 Block C July 7 July 18 July 24 2007- Day 7 Infection July 25 July 19 July 31 2007- Harvest Dates Experimental Design

• Slaughter lambs at 3, 5, and 7 d

after infection

• Sample abomasal mucosa & abdominal

lymph nodes

Abomasal Lymph Nodes

Abmasal Lymph Node Count 2 4 6 8 10 3 5 7 #LN Lymph Node Weight 2 4 6 8 3 5 7 Days PI WT (g) Hair Wool

• Lymph node weight: significant effects of type and

day*type interaction (p=0.004)

White Blood Cell Counts

b: Lymphocytes

2000 4000 6000 8000 10000 3 5 7 Days PI cells / μ l

d: Neutrophils

1000 2000 3000 4000 5000 3 5 7 Days PI cells / μ l * * * c: 50 100 150200 250300 3 5 7 D H W cells / μ l a 2000 4000 6000 8000 10000 12000 14000 3 5 7 D cells / μ l *

PMN: model (p=0.0231), type (p=0.0003), day (p=0.2155)

Histology

A 200 400 600 8001000 1200 1400 1600 1800 3 5 7 D

cells/mm2

H W

• By day 3, there is a noticeable difference in tissue

neutrophils

• Are neutrophils playing a role in early immune response to

Haemonchus contortus?

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IL-4 in abomasal mucosa at 0, 3, 5, & 7 days postinfection

20 40 60 80 3 5 7 Fold Change

(A) IL-4

3 5 7 Fold Change

(B) IL-13

1 2 3 4 3 5 7 Fold Change Days after infection

(C) IL-33

Hair Wool * 3 5 7 Fold Change Days after infection Hair Wool

IL-13 and IL-33 in abomasal mucosa at 0, 3, 5, & 7 days postinfection

3 5 7 Fold Change

(A) IL-4

1 2 3 3 5 7 Fold Change

(B) IL-13

3 5 7 Fold Change Days after infection

(C) IL-33

Hair Wool ***

20 40 60 3 5 7 Fold Change 3 5 7 Fold Change

(B) IL-13

1 2 3 4 3 5 7 Fold Change Days after infection

(C) IL-33

Hair Wool ***

3 5 7 3 5 7 Fold Change Days after infection

(C) IL-33

Hair Wool

IL-4, IL-13 and IL-33 in abomasal mucosa at 0, 3, 5, & 7 days after infection

20 40 60 80 3 5 7 Fold Change

(A) IL-4

1 2 3 3 5 7 Fold Change

(B) IL-13

1 2 3 4 3 5 7 Fold Change Days after infection

(C) IL-33

Hair Wool * *** ***

FEC EBVs of sires with 10 or more progeny and minimum FEC EBV accuracy of 0.80 (N = 94)

• 200
• 150
• 100
• 50

50 100 150 200 250 300 Sires Average PFEC EBV, %

Genomics: genotype 100 progeny-tested Katahdin rams using 700K SNP chip ≥

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http://www.toledotel.com/~smokeyvly/sheep6%20004.jpg

Questions?