Nested Clade Analysis

1
Nested Clade Analysis
2
Nested Clade Analysis

• In 1987 Published The Nested Clade Method For
  Using A Haplotype Tree As A Tool For Discovering
  Gene/Phenotype Associations
• Nests The Haplotypes in Tree Into Evolutionary
  Clades (Branches)
• The Resulting Nested Design Provides Framework
  For Detecting Phenotypic Associations.
• Tests The Hypothesis That Haplotypes Or Clades
  Are Randomly Distributed In The Network With
  Respect To Phenotypes

From Templeton bioinfo.cs.technion.ac.il/forum/tem
pleton_haplotype_tree.ppt
3
The Drosophila Adh Haplotype Tree
4
The Drosophila Adh Haplotype Tree
1-6
1-11
1-10
1-7
1-1
1-2
1-9
1-3
1-5
1-8
1-4
5
The Drosophila Adh Haplotype Tree
2-5
2-3
2-1
2-4
2-2
6
The Drosophila Adh Haplotype Tree
3-1
3-2
7
Results of Nested Analysis of Variance of Adh
Activity Using The Adh Haplotype Tree




Significant 0.1 Level
Significant at 1 Level
8
Functional Allelic Categories from the Nested
Analysis of Variance of Adh Activity




9
(No Transcript)
10
Phenotypic Distributions Identified Though
Nested Clade Analysis
11
Nested Clade Analyses

• Greater Statistical Power By Focusing On Fewer
  Comparisons
• Greater Biological Power In Detecting Mutations
  With Phenotypic Effects
• Deals With High Levels of Genetic Variation
  Through Pooling Into Clades
• Useful In Ultimately Identifying Causative
  Mutations

12
Extension of NCA to phylogeography

• Substitute geographical differences for
  phenotypic differences
• Creates landscape approach to haplotype network
• Tests hypothesis that haplotypes are randomly
  distributed geographically with respect to those
  they are nested with in the network (null no
  association between geography and clades)

13
(No Transcript)
14

• If null is rejected, step-down inference key is
  used to determine mechanisms behind association
  (key)
• Problem (Knowles and Maddison, 2002) NCA does
  not consider stochasticity (random error) in its
  approach, unlike coalescent-based models or AMOVA
• Created simluated data sets with known
  genealogies
• NCA repeatedly misidentified the stochastic
  process of lineage sorting, and instead,
  incorrectly assigned a deterministic process to
  patterns of genetic variation in 70 of the data
  sets.
• Templeton created new key in 2003

15
Testing via metaanalysis
16
(No Transcript)