\u25a0Computational approaches to study Genetics<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n<\/figure>\n\n\n\n<\/figure>\n\n\n\n<\/figure>\n\n\n\n<\/figure>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Aim of Buckwheat Project<\/strong><\/h3>\n\n\n\n
Collect & maintain genetic resources of buckwheat-related species (many wild species are facing extinction due to development)<\/li>
Understand domestication process of buckwheat<\/li>
Identify genes important for breeding of buckwheat<\/li><\/ul>\n\n\n\n
\u201cExtensive characterization of domestication-related genes in buckwheat by utilizing the genetic resource of Yunnan province, China\u201d
KAKENHI Fostering Joint International Research B, PI: Yasuo Yasui (Kyoto U)
\u25a0Why am I involved?<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
Huge advance in technology to generate large-scale DNA data<\/li>
Need for people with computational skills and knowledge of genetics (very few such people that work on buckwheat, horses, etc)<\/li><\/ul>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Outline<\/strong><\/h3>\n\n\n\n
Basic concepts of genetics and evolution<\/mark><\/strong><\/li>
What is written in the DNA?<\/li>
How can we know what\u2019s written in the DNA?<\/li>
How can we associate \u201cgenotype\u201d with \u201cphenotype\u201d?
Research on Thoroughbred horses<\/li><\/ul><\/li><\/ul>\n\n\n\n
\u25a0History of Abstraction in Biology<\/strong><\/h3>\n\n\n\n
Biology is\u2026 complex, diverse, changes over time<\/p>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Basic concepts of genetics<\/strong><\/h3>\n\n\n\n
Parent and offspring are similar \u2013 genetic information is passed on What is passed on and how?<\/li><\/ul>\n\n\n\n<\/figure>\n\n\n\n
Information of A and a is transmitted across generations without changing<\/li>
The \u201cphenotype\u201d (appearance) of AA and Aa are the same<\/li><\/ul>\n\n\n\n
\u25a0Mechanism of Heredity<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
Genome:<\/mark><\/strong> entire set of genetic information Every human has 2 genomes (1 from each parent)<\/p>\n\n\n\n
<\/div>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Large variation in genome size<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Mutation<\/strong><\/h3>\n\n\n\n
\u201cReplication\u201d cannot generate diversity, genetic information changes<\/p>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Evolution<\/strong><\/h3>\n\n\n\n
Heredity<\/li>
Mutation => some of them change the \u201cphenotype\u201d<\/li>
\u201cPopulation process\u201d (competition, \u201cstruggle for survival\u201d)<\/li><\/ul>\n\n\n\n<\/figure>\n\n\n\n
Many individuals do not produce any offspring We can\u2019t observe mutations in those individuals
Do all individuals have equal chance to produce offspring? <\/mark><\/strong> Did the mutation change the chance to produce offspring?<\/mark><\/strong><\/p>\n\n\n\n
\u25a0Outline<\/strong><\/h3>\n\n\n\n
Basic concepts of genetics and evolution<\/li>
What is written in the DNA?<\/mark><\/li>
How can we know what\u2019s written in the DNA?<\/li>
How can we associate \u201cgenotype\u201d with \u201cphenotype\u201d?
Research on Thoroughbred horses<\/li><\/ul><\/li><\/ul>\n\n\n\n
\u25a0What is written in the genome?<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
All cells contain the same set of genes The amount and timing of RNA\/proteins produced differ (very complicated process)<\/p>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Proteins as amino acid sequences<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
\u21d2Many genes share high similarity across distantly related species<\/mark><\/p>\n\n\n\n
often harmful, sometimes beneficial<\/li><\/ul>\n\n\n\n
\u25a0A lot of unnecessary information in the genome!?<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
\u201cSo much Junk DNA in our Genome\u201d (Susumu Ohno, 1972) We all acquire ~100 new mutations but most of us are fine (i.e. most mutations are harmless)<\/p>\n\n\n\n
\u201cJunk DNA\u201d should be removed during evolution!?!?<\/p>\n\n\n\n
each \u201cjunk\u201d is removed but lots of \u201cjunk\u201d are being generated<\/li>
they are parasites that try to survive themselves<\/li><\/ul>\n\n\n\n
\u25a0Outline<\/strong><\/h3>\n\n\n\n
Basic concepts of genetics and evolution<\/li>
What is written in the DNA?<\/li>
How can we know what\u2019s written in the DNA?<\/mark><\/strong><\/li>
How can we associate \u201cgenotype\u201d with \u201cphenotype\u201d?
Research on Thoroughbred horses<\/li><\/ul><\/li><\/ul>\n\n\n\n
\u25a0How do we know the sequence of the genome?<\/strong><\/h3>\n\n\n\n
Genome sequencing and assembly<\/li><\/ul>\n\n\n\n<\/figure>\n\n\n\n
\u25a0How can we \u201cfind\u201d the genes?<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
Extract RNA, sequence, and \u201cmap\u201d them to the genome Not so simple because of many similar genes and the presence of introns<\/p>\n\n\n\n
Search for similar sequences in the genome Most genes in 1 species have similar genes in other species Similar genes are likely to have similar functions<\/p>\n\n\n\n
\u25a0How can we \u201cfind\u201d the genes?<\/strong><\/h3>\n\n\n\n
Predict genes based on their features<\/p>\n\n\n\n<\/figure>\n\n\n\n
Nucleotide composition is statistically different protein-coding sequence vs non-coding sequences, introns GT-AG of intron vs GT-AG not associated with introns<\/p>\n\n\n\n
\u25a0Outline<\/strong><\/h3>\n\n\n\n
Basic concepts of genetics and evolution<\/li>
What is written in the DNA?<\/li>
How can we know what\u2019s written in the DNA?<\/li>
How can we associate \u201cgenotype\u201d with \u201cphenotype\u201d?<\/mark>
Research on Thoroughbred horses<\/mark><\/li><\/ul><\/li><\/ul>\n\n\n\n
\u25a0Domestication of Horses (~5500 yrs ago)<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Many diverse breeds established after domestication<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
Thoroughbreds<\/mark><\/strong>
Originated in 18th Century (3 \u201cfounder\u201d stallions)<\/li>
Horses that win races are selected to breed in many different countries<\/li><\/ul><\/li><\/ul>\n\n\n\n
\u25a0Selective breeding of Thoroughbreds in Japan<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
~7000 horses are born and registered at JRA (Japan Racing Association)<\/li>
Only 10-20 males per generation (>50% of females) are selected for breeding<\/li><\/ul>\n\n\n\n
\u21d2Thoroughbreds are much faster than other horse breeds due to selective breeding for 20-30 generations<\/mark><\/strong><\/p>\n\n\n\n
==><\/mark> but, genetic information has not been utilized yet<\/p>\n\n\n\n
\u25a0Many differences between wild and cultivated Buckwheat<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Process of domestication<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
Mutations occur that result in a desirable trait (might already exist in wild, or occur afterwards)<\/li>
Humans preferentially select and breed those individuals<\/li>
Can we identify the mutations selected by humans? <\/mark><\/strong>(should speed up the selective breeding)<\/li>
Can we identify other useful mutations\/genes that could be useful for breeding?<\/mark><\/strong><\/li><\/ul>\n\n\n\n
\u25a0Variation in the DNA of each individual<\/strong><\/h3>\n\n\n\n
Single Nucleotide Polymorphism (SNP)<\/p>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Example of variation (SNP) associated with racing ability<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
SNP in myostatin gene affects optimum racing distance<\/p>\n\n\n\n
\u25a0Using genetic information for Thoroughbred breeding<\/strong><\/h3>\n\n\n\n
\u21d2Can evaluate the genetic potential of each horse<\/strong> ==> more informed choice of which horse to keep and which to discard<\/p>\n\n\n\n
\u21d2Can identify the best breeding (male x female) combination<\/strong> ==> more informed choice of which male and female to mate<\/p>\n\n\n\n<\/figure>\n\n\n\n
~400 Thoroughbred horses from JRA (Currently extended to ~1000 samples)<\/li>
Can we identify genetic variation associated with variation in traits?<\/mark><\/li>
Can we identify genetic variation associated with variation in racing ability?<\/mark><\/li><\/ul>\n\n\n\n
\u25a0Genome-wide Association Study (GWAS)<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
SNPs in neighboring region are \u201clinked\u201d<\/p>\n\n\n\n
\u25a0GWAS works with coat color genes (proof of concept)<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Genomic signatures of selection<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Regions of reduced diversity regions in Thoroughbreds<\/strong><\/h3>\n\n\n\n<\/figure>\n\n\n\n
\u25a0Computational approaches to identify important regions<\/strong><\/h3>\n\n\n\n
Genome-wide association studies very powerful when there is a targeted, simple trait<\/li>
Genomic signature of artificial\/natural selection can use also for complex traits and where there is no specific trait
Difficult to pinpoint actual causative mutation\/gene<\/li>
Can identify candidate regions\/genes that can be tested experimentally<\/li><\/ul><\/li><\/ul>\n\n\n\n
\u25a0Summary<\/strong><\/h3>\n\n\n\n
We can explain the process creating the diversity of life in a common mathematical\/computational framework<\/li>
We can apply the same approaches to study many different species (e.g. horses, buckwheat)<\/li>
Computational\/mathematical approaches are becoming more important with the increase of data<\/li>
More advanced mathematics are needed to go from \u201csequences\u201d to complex networks, shapes, 3D structures etc?<\/li><\/ul>\n\n\n\n
\u25a0Acknowledgements<\/strong><\/h3>\n\n\n\n
Thoroughbred project<\/strong> Hideki Innan, Takahiro Sakamoto, Watal M Iwasaki (SOKENDAI), Fumio Sato (JRA Hidaka), Teruaki Tozaki (Lab of Racing Chemistry), Takao Suda (Journalist), etc<\/li>
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