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Slide 1: Title Slide
Extrachromosomal Inheritance
Slide 2: Introduction to Extrachromosomal Inheritance
Definition: Extrachromosomal inheritance refers to the transmission of genetic material that is not found within the nucleus.
Key Components: Involves genes located in mitochondria, chloroplasts, and plasmids.
Slide 3: Mitochondrial Inheritance
Mitochondria: Organelles responsible for energy production.
Mitochondrial DNA (mtDNA): Circular DNA molecule found in mitochondria.
Inheritance Pattern: Maternally inherited, meaning it is passed from mothers to all their offspring.
Diseases: Examples include Leber’s hereditary optic neuropathy (LHON) and mitochondrial myopathy.
Slide 4: Chloroplast Inheritance
Chloroplasts: Organelles responsible for photosynthesis in plants.
Chloroplast DNA (cpDNA): Circular DNA molecule found in chloroplasts.
Inheritance Pattern: Often maternally inherited in most plants, but can vary in some species.
Examples: Variegation in plants, where leaf color patterns are determined by chloroplast DNA.
Slide 5: Plasmid Inheritance
Plasmids: Small, circular DNA molecules found in bacteria and some eukaryotes.
Features: Can carry antibiotic resistance genes and can be transferred between cells through processes like conjugation.
Significance: Important in biotechnology for gene cloning and genetic engineering.
Slide 6: Mechanisms of Extrachromosomal Inheritance
Non-Mendelian Patterns: Do not follow Mendel’s laws of inheritance.
Cytoplasmic Segregation: During cell division, organelles like mitochondria and chloroplasts are randomly distributed to daughter cells.
Heteroplasmy: Presence of more than one type of organellar genome within a cell, leading to variation in expression.
Slide 7: Examples of Extrachromosomal Inheritance
Four O’clock Plant (Mirabilis jalapa): Shows variegated leaves due to different cpDNA in leaf cells.
Petite Mutants in Yeast: Result from mutations in mitochondrial DNA affecting respiration.
Slide 8: Importance of Extrachromosomal Inheritance
Evolution: Provides insight into the evolution of eukaryotic cells.
Medicine: Understanding mitochondrial inheritance helps in diagnosing and treating mitochondrial diseases.
Agriculture: Chloroplast inheritance can be used in plant breeding and genetic modification.
Slide 9: Recent Research and Advances
Gene Editing: Techniques like CRISPR-Cas9 are being used to edit mitochondrial and chloroplast DNA.
Therapies: Development of mitochondrial replacement therapy (MRT) for preventing mitochondrial diseases.
Slide 10: Conclusion
Summary: Extrachromosomal inheritance involves the transmission of genetic material outside the nucleus and plays a crucial role in genetics, medicine, and biotechnology.
Future Directions: Continued research and technological advancements hold promise for new treatments and applications.
Slide 11: Questions and Discussion
Invite Audience: Open the floor for any questions or further discussion on the topic.
Introduction:
RNA interference (RNAi) or Post-Transcriptional Gene Silencing (PTGS) is an important biological process for modulating eukaryotic gene expression.
It is highly conserved process of posttranscriptional gene silencing by which double stranded RNA (dsRNA) causes sequence-specific degradation of mRNA sequences.
dsRNA-induced gene silencing (RNAi) is reported in a wide range of eukaryotes ranging from worms, insects, mammals and plants.
This process mediates resistance to both endogenous parasitic and exogenous pathogenic nucleic acids, and regulates the expression of protein-coding genes.
What are small ncRNAs?
micro RNA (miRNA)
short interfering RNA (siRNA)
Properties of small non-coding RNA:
Involved in silencing mRNA transcripts.
Called “small” because they are usually only about 21-24 nucleotides long.
Synthesized by first cutting up longer precursor sequences (like the 61nt one that Lee discovered).
Silence an mRNA by base pairing with some sequence on the mRNA.
Discovery of siRNA?
The first small RNA:
In 1993 Rosalind Lee (Victor Ambros lab) was studying a non- coding gene in C. elegans, lin-4, that was involved in silencing of another gene, lin-14, at the appropriate time in the
development of the worm C. elegans.
Two small transcripts of lin-4 (22nt and 61nt) were found to be complementary to a sequence in the 3' UTR of lin-14.
Because lin-4 encoded no protein, she deduced that it must be these transcripts that are causing the silencing by RNA-RNA interactions.
Types of RNAi ( non coding RNA)
MiRNA
Length (23-25 nt)
Trans acting
Binds with target MRNA in mismatch
Translation inhibition
Si RNA
Length 21 nt.
Cis acting
Bind with target Mrna in perfect complementary sequence
Piwi-RNA
Length ; 25 to 36 nt.
Expressed in Germ Cells
Regulates trnasposomes activity
MECHANISM OF RNAI:
First the double-stranded RNA teams up with a protein complex named Dicer, which cuts the long RNA into short pieces.
Then another protein complex called RISC (RNA-induced silencing complex) discards one of the two RNA strands.
The RISC-docked, single-stranded RNA then pairs with the homologous mRNA and destroys it.
THE RISC COMPLEX:
RISC is large(>500kD) RNA multi- protein Binding complex which triggers MRNA degradation in response to MRNA
Unwinding of double stranded Si RNA by ATP independent Helicase
Active component of RISC is Ago proteins( ENDONUCLEASE) which cleave target MRNA.
DICER: endonuclease (RNase Family III)
Argonaute: Central Component of the RNA-Induced Silencing Complex (RISC)
One strand of the dsRNA produced by Dicer is retained in the RISC complex in association with Argonaute
ARGONAUTE PROTEIN :
1.PAZ(PIWI/Argonaute/ Zwille)- Recognition of target MRNA
2.PIWI (p-element induced wimpy Testis)- breaks Phosphodiester bond of mRNA.)RNAse H activity.
MiRNA:
The Double-stranded RNAs are naturally produced in eukaryotic cells during development, and they have a key role in regulating gene expression .
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Application of nuclear and genomic technologies for improving livestock productivity in developing world: Challenges and opportunities
1. Better lives through livestock
Application of nuclear and genomic technologies for improving livestock
productivity in developing world: Challenges and opportunities
Prof. Raphael Mrode
Principal Scientist
Livestock Genetics Program
IAEA International Symposium on Sustainable Animal
Production and Health – Current Status and Way Forward
Vienna. 28 June – 2nd July, 2021
2. 2
Outline of the talk
• Major drivers for the success of genomic technologies in developed countries
• Opportunities in developing countries
• Limited data infrastructure, genomic tools
• Understanding and utilization of genetic basis of adaptation in
indigenous livestock
• Indirect opportunities for improving animal feeds
• Challenges
• Data capture, Cost efficiency
• Adequacy of commercial genomic tools and delivery of superior
genetics
• Conclusions
3. 3
• Benefits of genomic selection have well been
demonstrated in developed countries
• Higher rates of genetic gain
• Reduced generation interval especially in dairy
cattle
• Accuracies of above 70% for production traits
reported for young genomic proven bulls
• High accuracies for cows for low heritability traits
• Enabled genetic improvement in difficult to
measure traits/predictive traits which are of
global importance
Benefits of genomic technologies in developed
countries
4. 4
Proportion of inseminations to various categories
of bulls: 2011-2018 in USA (Wiggans, 2019)
48 51 54
58
63
67 69 67
0
0
0
0
0
0 0
0
39
39 37
33
31
28 29 31
11 8 9 9 6 4 2 2
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
2011 2012 2013 2014 2015 2016 2017 2018
Year
Young genotyped
Young non-genotyped
1st crop genotyped
1st crop non-genotyped
Old genotyped
Old non-genotyped
5. 5
Enabling factors for huge success in genomic
selection in developed countries
• Existence of well-established infrastructure
• Routine data capture systems Genetic
evaluation Delivery system for superior
genetics
• Major drivers : Dairy Cattle - multi-national AI
companies; Beef cattle &Sheep - driven by
breed societies; Pigs and Poultry -- driven
private breeding companies
6. 6
Enabling factors for huge success in genomic
selection in developed countries
• Organization and design
• Across country collaboration: Euro-Genetics ,
North America Consortium
• Inter-genomics : Brown Swiss
• Strategic genotyping of connected herds to
handle difficult to measure traits – Australia AGIN
• Huge role of farmer: genomics designed to
address farmer’s needs
• USA genotyped cows: 2015 =350K & 2020 = 900K
• Selection - which calves to keep, cows to flush,
breed with sexed semen ; Pedigree
validation/determination; mating
7. 7
• Should be examined:
• Not only in terms of the direct application of
the principles of genomic technologies
• But also, the important associated factors:
infrastructure, design, organization, and
farmers’ role
Opportunities and challenges of genomic
technologies in developing countries
8. 8
• Lack of routine pedigree recording system
• Genomic prediction using the G matrix—less
reliance on pedigree
• Limited herd sizes - animal effect confounded
with herd effects
• Use of haploblocks from G matrix from
common sires used across herds (Powell et al,
2018)
Some limiting data infrastructure in developing
countries & quick wins of genomics
9. 9
• The African Dairy Genetics Gain (ADGG) Project
at ILRI funded by BMGF and working in several
African countries
• Tanzania data to illustrate of quick wins of
genomics
• Genomic prediction on about 2000 animals
genotyped with HD SNP chip
• Limited pedigree: 88%, 11.4%and 0.6% with
no, one and both parents identified
• More than 50% cows in one herd
Quick wins of genomics: Illustration with using
Tanzania data
10. 10
Genetic parameters from a fixed (FRM)and random regression (RRM)
model with G matrix for Tanzania data
Trait
Model
Heritability Variance due
to Pe
Variance due
to herd
Phenotypic
Variance
Milk Yield FRM GBLUP 0.12±0.03 0.10±0.03 0.23±0.02 9.73±0.19
ssGBLUP 0.12±0.03 0.12±0.03 0.22±0.02 9.68±0.16
RRM GBLUP 0.22 0.14 0.21 9.76
ssGBLUP 0.24 0.15 0.21 9.72
Body
Weight
FRM GBLUP 0.24±04 0.20±0.04 0.22±0.03 1287.6±33.2
ssGBLUP 0.22±04 0.22±04 0.26±03 1338.4±29.9
11. 11
Forward validation results for daily milk yield(kg) and body weight(kg)
Trait Method Correlation Regression
Milk yield FRM-GBLUP 0.57 1.1
FRM-ssGBLUP 0.59 1.0
RRM-GBLUP 0.55 1.0
RRM-ssGBLUP 0.53 0.92
Body weight FRM-GBLUP 0.83 1.0
FRM-ssGBLUP 0.77 1.1
12. 12
• Fernandes Júnior et al. (2016) examined genomic
prediction for carcass traits (rib eye area (REA) ,back fat
thickness (BF), and hot carcass weight (HCW) in Brazilian
Nellore cattle
• Total of 1756 steers genotyped with 777K HD Chip.
• Accuracies estimates were of low-medium 0.21 (BT),
0.37 (HCW) and 0.46 (REA) when using YD
• Silva et al 2016--- GS in experimental farm with 788 Nellore
animals genotyped with HD but with 9551 with pedigree
• Accuracies for FCR and RFI : 0.30 to 0.45 from
ssGBLUP compared to 0.29 to 0.23 from BLUP
Similar genomic predictions in Beef cattle
13. 13
• Inadequate data structure ( small data sets and
small sire progeny size)
• The application appropriate genomic
methodologies
• Incorporation of external genomic information
Some limiting data infrastructure in developing
countries & quick wins of genomics
14. 14
• Inadequate data structure
• For example, the Simmental-Simbrah beef cattle
population is one of the largest under genetic
evaluation in Mexico
• In the 2010 run, 5,159 bulls were evaluated but
only 703 Simmental and 387 Simbrah with more
than 10 daughters
• The application of Single step methodology
implies bulls with reliable evaluations are not
critical
Some limiting data infrastructure : The application
appropriate genomic methodology
15. 15
• Cows can now be genotyped to
• Increase reference populations
• Strategically handle difficult to
measure traits
• Single Step genomic methods can be used
to compute evaluations using both pedigree
and genomic information.
• Bayesian methods could also be considered
Some limiting data infrastructure : The application
appropriate genomic methodology
16. 16
Some limiting data infrastructure :Incorporation external information
• Across country or regional opportunities : Brown swiss
model or SNP-BLUP model or consortium model
• Incorporating genotypes from foreign sires
17. 17
Across country or regional opportunities
• Pool genotypes to form a single reference
population
• InterGenomics : Brown Swiss populations
from 7 main countries
• InterGenomics-Holstein: Countries with
small Holstein populations (Israel, Ireland,
Slovenia, South Korea)
• Share genotypes: Eurogenetics & North
America Consortium with UK & Italy
• Pooling genomic data across countries
may be critical for GS in developing
countries
18. 18
• Li et al 2016 examined the improvement in
prediction reliabilities for 3 production traits in
Brazilian Holsteins that had no genotypes
• adding information from Nordic and French
Holstein bulls that had genotypes.
• Increases in reliabilities in some traits varied from
4 to 64%
• Similar studies in China Holstein with increase
in reliabilities from 0.266 to 0.330 from
incorporating Nordic bulls (Ma et al 2014)
Incorporating genotypes from foreign sires
19. 19
• Low density SNP assay (200) developed for breed
composition determination (Strucken et al , 2017)
• If parentage verification is included, assay expands
to 400 SNPs
Genomic tools: Breed composition and
parentage verification
20. 20
• Indigenous breeds represent a unique set
genotypes adapted to surviving under harsh
conditions and are disease/parasite resistance.
• Genomics provide the means for
understanding the genetic basis of this
adaptation
• Kwondo et al 2020 - Several loci in African
cattle related immunity, heat-tolerance
trypanotolerance and reproduction-related
genes.
Understanding and utilization of genetic basis of
adaptation in indigenous livestock
21. 21
• Small ruminants -- adaptation to arid
environments and resistance to endoparasites
in sheep from Tunisia (Ahbara et al, 2021)
• Paths for utilization
• Incorporation of functional regions/genes in
genomic prediction --- BayesR
• Gene editing & surrogate sires
Understanding and utilization of genomic basis of
adaptation in indigenous livestock
22. 22
Validated selection for stover quality without cost to grain
yield
• Using genomic prediction as a tool to improve stover traits- (in-vitro organic
matter digestibility (IVOMD) and metabolizable energy (ME))
• Supports the development of new dual-purpose maize varieties.
Vinayan, M.T., Seetharam, K., Babu, R. et al. Genome wide association study and genomic prediction for stover quality traits in tropical maize (Zea mays L.). Sci
Rep 11, 686 (2021). https://doi.org/10.1038/s41598-020-80118-2
Marker Density
(SNPs)
Traits
IVOMD% ME (MJ/kg)
200 0.36 0.42
500 0.42 0.43
1000 0.43 0.45
3000 0.44 0.46
100000 0.45 0.46
23. 23
Genomic selection in tropical forage grasses
e.g. Napier grass
• Five times more biomass than natural
pastures
• Increased yield when intercropped with
legumes and irrigated
• GWAS/Marker Assisted Selection under
development
• Agronomic performance and nutritional
qualities
PCA biplot of 84 accession showing yield traits
24. 24
• “In the age of the genotype [genomics],
phenotype is king”- Mike Coffey
• Several digital tool being pioneered
• ODK on Tablet and smart phone : ADGG & ICow
• Farmer-based systems – suitable for USSD phones
• Multi-component software, on dedicated “data
loggers” and mobile phones - BAIF-India
• AniCloud and AniCapture – CBBP (offline data
capture)
• Sensors to capture novel phenotypes on
fertility (Muasa et al, 2019)
The challenge of reliable systems for data
collection
25. 25
Genetic parameters and accuracy of prediction using part-lactation data
100 DIM 200 DIM 300 DIM 400 DIM 500 DIM
N 4400 8886 13177 17005 19599
Heritability 0.19±0.05 0.17±0.04 0.16±0.04 0.14±0.03 0.11±0.03
Rank correlations of gEBVs with those from 500 DIM
All Bulls (702) 0.87 0.93 0.97 0.99
Top 20% 0.30 0.61 0.75 0.79
Genetic prediction of 276 young animals born after 2014
with records excluded
Accuracy 0.44 0.52 0.54 0.57 0.58
Regression 0.83 0.95 0.97 1.04 1.06
26. 26
Challenge of adequacy commercial SNP array:
Examined in three African cattle
• Uniqueness genotypes of indigenous breeds leads to another
challenge; adequacy of commercial SNPs panels
27. 27
Assessment of the 23 commercial Bovine SNP arrays in 3 cattle breeds
0
5
10
15
20
25
30 Proportions of WGS in high correlation with array SNPs
Boran Ndama Holstein
Proportion
of
WGS
SNPS
28. 28
• Currently, most genotyped animals are females
• an outcome of development projects
• Breed societies in some cases in Brazil
• Lack of major drivers AI and breeding
companies and breed societies
• Most cases, samples sent abroad for genotyping
• Approaches needed to increase cost efficiency
for wide application of genomics
Cost efficiency of genomics
29. 29
• One stop shop with modern breeding
technologies and marker service laboratory ,
data management and analyses.
• Bundled genomic services to individual farmers
and farmer organizations : determination of
parentage, breed composition, genomic
selection and mating services
Cost efficiency of genomics
30. 30
• Cost efficiency increases when genomics is
combined with reproductive technologies.
• Use of sexed semen of genomically proven young
bulls
• Beef cattle : use of IVF, with embryos from
genotyped donors gave 79% higher genetic gain
(Carvalheiro, 2014 )
Cost efficiency of genomics
31. 31
• AI uptake still low and widespread use of local
bulls
• Therefore, genomic prediction must be
extended to local bulls - ADGG
• Improvement in AI services
• Work with the countries NAIC, breed societies
and farmer organization.
• Understanding the breeding structure—CBBP
for small ruminants and exploiting that
Deliverance of Improved genetics from genomics
32. 32
• Genomics offers quick wins for developing
countries: genomic prediction, parentage
discovery reducing need for accurate pedigree.
• Offers opportunity for across country or regional
collaboration; this will be needed to ensure
adequate data and best sires can be used across
regions
• In general, genotypic data offers opportunities to
model underling genetics for resilience traits
Conclusions
33. 33
• Bundled genomic services in combination with
reproductive technologies will needed to improve
cost-efficiency and widespread application of GS
• Of great importance is an efficient delivery
mechanism needs to be in place for the superior
genetics
Conclusions
34. 34
Dr Okeyo Mwai Dr Chris Jones (ILRI)
Prof. John Gibson Dr Abdulfatai Tijjani (ILRI)
Dr Julie Ojango Dr Joram Mwacharo
Dr Chinyere Ekine-Dzivenu Prof. Olivier Hanotte
Acknowledgements