1 . Question 1 pgm-1 locus

1.1 . Create data frame of observed values

dat <- data.frame(AA = c(634), Aa = c(391), aa = c(85), row.names = c("observed genotype counts"))
Warning messages:
1: In scan(file = file, what = what, sep = sep, quote = quote, dec = dec,  :
  EOF within quoted string
2: In scan(file = file, what = what, sep = sep, quote = quote, dec = dec,  :
  EOF within quoted string
3: In scan(file = file, what = what, sep = sep, quote = quote, dec = dec,  :
  EOF within quoted string
4: In scan(file = file, what = what, sep = sep, quote = quote, dec = dec,  :
  EOF within quoted string
dat

1.2 . Calculate allele frequencies to work out expected genotype

proportions (e.g. 1 = p^2+q^2+2pq)
allele_freq <- cbind(((2*dat$AA) + dat$Aa)/(2*rowSums(dat)),
  ((2*dat$aa) + dat$Aa)/(2*rowSums(dat)))
  colnames(allele_freq) <- c("A", "a")
allele_freq
                                 A         a
observed genotype counts 0.7472973 0.2527027

1.3 . Calculate expected genotype proportions under Hardy-Weinberg Equillibrium

HWEexpected <- t(apply(allele_freq, 1, function(x){
  AA <- x["A"]^2
  Aa <- 2*x["A"]*x["a"]
  aa <- x["a"]^2
  return(cbind(AA, Aa, aa))
  }))
HWEexpected
                              [,1]      [,2]       [,3]
observed genotype counts 0.5584533 0.3776881 0.06385866

1.4 . Chisquare test for observed vs expected HWE values

# convert genotypes and proportions into lists for efficient tests
dat <- lapply(1:nrow(dat), function(i) return(as.vector(dat[i,])))
HWEexpected <- lapply(1:nrow(HWEexpected), function(i){
return(as.vector(HWEexpected[i,]))
})
# Run HWE test
mapply(FUN = chisq.test, x = dat, p = HWEexpected, SIMPLIFY = FALSE)
[[1]]

    Chi-squared test for given probabilities

data:  dots[[1L]][[1L]]
X-squared = 5.0344, df = 2, p-value = 0.08068

The p-value is greater than 0.05 so we fail to reject the null hypothesis that the population is in Hardy-Weinberg Equilibrium

2 . Question 2 Serum Haptotypes in Egyptians

2.1 . Create data frame of observed values

dat2 <- data.frame(pp = c(9), pq = c(135), pr = c(2), qq = c(75),  qr = c(39), rr = c(25), row.names =
                    c("observed genotype counts"))
dat2

2.2 . Calculate allele frequencies to work out expected genotype

proportions (e.g. 1 = p^2+q^2+2pq)
allele_freq <- cbind(((2*dat2$pp) + dat2$pq + dat2$pr)/(2*rowSums(dat2)),
   ((2*dat2$qq) + dat2$pq + dat2$qr)/(2*rowSums(dat2)),
  ((2*dat2$rr) + dat2$pr + dat2$qr)/(2*rowSums(dat2)))
colnames(allele_freq) <- c("p", "q", "r")
row.names(allele_freq) <- c("gene frequency")
allele_freq
                       p         q         r
gene frequency 0.2719298 0.5684211 0.1596491

2.3 . Calculate expected genotype proportions under Hardy-Weinberg Equillibrium

HWEexpected <- t(apply(allele_freq, 1, function(x){
  pp <- x["p"]^2
  pq <- 2*x["p"]*x["q"]
  pr <- 2*x["p"]*x["r"]
  qq <- x["q"]^2
  qr <- 2*x["q"]*x["r"]
  rr <- x["r"]^2
  return(cbind(pp, pq, pr, qq, qr, rr))
  }))
colnames(HWEexpected) <- c("pp", "pq", "pr", "qq", "qr", "rr")
HWEexpected
                       pp        pq         pr        qq        qr         rr
gene frequency 0.07394583 0.3091413 0.08682672 0.3231025 0.1814958 0.02548784

2.4 . Chisquare test for observed vs expected HWE values

# convert genotypes and proportions into lists for efficient tests
dat2 <- lapply(1:nrow(dat2), function(i) return(as.vector(dat2[i,])))
HWEexpected <- lapply(1:nrow(HWEexpected), function(i){
return(as.vector(HWEexpected[i,]))
})
# Run HWE test
mapply(FUN = chisq.test, x = dat2, p = HWEexpected, SIMPLIFY = FALSE)
[[1]]

    Chi-squared test for given probabilities

data:  dots[[1L]][[1L]]
X-squared = 102.39, df = 5, p-value < 2.2e-16

p-value is less than 0.05 so we reject the null of HWE.

3 . Question 3 M-N blood groups

3.1 . Create data frame of observed values

dat3 <- data.frame(M = c(475, 195, 896, 14), MN = c(89, 215, 1559, 48), N = c(5, 79, 645, 138), row.names = c("Eskimos", "Russians", "Belgians", "Papuans"))
dat3

3.2 . Calculate allele frequencies to work out expected genotype

proportions (e.g. 1 = p^2+q^2+2pq)

3.2.1 . Eskimos

allele_freq_esk <- cbind(((2*dat3[1,1]) + dat3[1,2])/(2*sum(dat3[1,])),
  ((2*dat3[1,3]) + dat3[1,2])/(2*sum(dat3[1,])))
  colnames(allele_freq_esk) <- c("M", "N")
allele_freq_esk
             M          N
[1,] 0.9130053 0.08699473

3.2.2 . Russians

allele_freq_rus <- cbind(((2*dat3[2,1]) + dat3[2,2])/(2*sum(dat3[2,])),
  ((2*dat3[2,3]) + dat3[2,2])/(2*sum(dat3[2,])))
  colnames(allele_freq_rus) <- c("M", "N")
allele_freq_rus
             M         N
[1,] 0.6186094 0.3813906

3.2.3 . Belgians

allele_freq_bel <- cbind(((2*dat3[3,1]) + dat3[3,2])/(2*sum(dat3[3,])),
  ((2*dat3[3,3]) + dat3[3,2])/(2*sum(dat3[3,])))
  colnames(allele_freq_bel) <- c("M", "N")
allele_freq_bel
             M         N
[1,] 0.5404839 0.4595161

3.2.4 . Papuans

allele_freq_pap <- cbind(((2*dat3[4,1]) + dat3[4,2])/(2*sum(dat3[4,])),
  ((2*dat3[4,3]) + dat3[4,2])/(2*sum(dat3[4,])))
  colnames(allele_freq_pap) <- c("M", "N")
allele_freq_pap
        M    N
[1,] 0.19 0.81

3.3 . Calculate expected genotype proportions under Hardy-Weinberg Equillibrium

3.3.1 . Eskimos

HWEexpected_esk <- t(apply(allele_freq_esk, 1, function(x){
  M <- x["M"]^2
  MN <- 2*x["M"]*x["N"]
  N <- x["N"]^2
  return(cbind(M,MN,N))
  }))
colnames(HWEexpected_esk) <- c("M", "MN", "N")
HWEexpected_esk
             M        MN           N
[1,] 0.8335786 0.1588533 0.007568083

3.3.2 . Russians

HWEexpected_rus <- t(apply(allele_freq_rus, 1, function(x){
  M <- x["M"]^2
  MN <- 2*x["M"]*x["N"]
  N <- x["N"]^2
  return(cbind(M,MN,N))
  }))
colnames(HWEexpected_rus) <- c("M", "MN", "N")
HWEexpected_rus
             M        MN         N
[1,] 0.3826776 0.4718636 0.1454588

3.3.3 . Belgians

HWEexpected_bel <- t(apply(allele_freq_bel, 1, function(x){
  M <- x["M"]^2
  MN <- 2*x["M"]*x["N"]
  N <- x["N"]^2
  return(cbind(M,MN,N))
  }))
colnames(HWEexpected_bel) <- c("M", "MN", "N")
HWEexpected_bel
             M        MN         N
[1,] 0.2921228 0.4967221 0.2111551

3.3.4 . Papuans

HWEexpected_pap <- t(apply(allele_freq_pap, 1, function(x){
  M <- x["M"]^2
  MN <- 2*x["M"]*x["N"]
  N <- x["N"]^2
  return(cbind(M,MN,N))
  }))
colnames(HWEexpected_pap) <- c("M", "MN", "N")
HWEexpected_pap
          M     MN      N
[1,] 0.0361 0.3078 0.6561

3.4 . Chisquare test for observed vs expected HWE values

3.4.1 . Eskimos

# convert genotypes and proportions into lists for efficient tests
dat3_esk <- lapply(1:nrow(dat3[1,]), function(i){return(as.vector(dat3[i,]))})
HWEexpected_esk <- lapply(1:nrow(HWEexpected_esk), function(i){return(as.vector(HWEexpected_esk[i,]))
})
# Run HWE test
mapply(FUN = chisq.test, x = dat3_esk, p = HWEexpected_esk, SIMPLIFY = FALSE)
Chi-squared approximation may be incorrect
[[1]]

    Chi-squared test for given probabilities

data:  dots[[1L]][[1L]]
X-squared = 0.13408, df = 2, p-value = 0.9352

Chi-squared doesn’t like low values #### . Check Eskimo chi-squared against r-package for Hardy-Weinberg

library(HardyWeinberg)
Loading required package: mice
Loading required package: lattice
Loading required package: Rsolnp
eskobs <- c(AA = 475, AB = 89, BB = 5)
HWChisq(eskobs)
Expected counts below 5: chi-square approximation may be incorrect
Chi-square test with continuity correction for Hardy-Weinberg equilibrium (autosomal)
Chi2 =  0.01751215 DF =  1 p-value =  0.8947205 D =  -0.693761 f =  0.01535081 

This test isn’t happy either… To the best that I can tell, Eskimos are in HWE for blood groups ### . Russians

# convert genotypes and proportions into lists for efficient tests
dat3_rus <- lapply(1:nrow(dat3[2,]), function(i){return(as.vector(dat3[i,]))})
HWEexpected_rus <- lapply(1:nrow(HWEexpected_rus), function(i){return(as.vector(HWEexpected_rus[i,]))
})
# Run HWE test
mapply(FUN = chisq.test, x = dat3_rus, p = HWEexpected_rus, SIMPLIFY = FALSE)
[[1]]

    Chi-squared test for given probabilities

data:  dots[[1L]][[1L]]
X-squared = 497, df = 2, p-value < 2.2e-16

Russians are not in HWE

3.4.2 . Belgians

# convert genotypes and proportions into lists for efficient tests
dat3_bel <- lapply(1:nrow(dat3[3,]), function(i){return(as.vector(dat3[i,]))})
HWEexpected_bel <- lapply(1:nrow(HWEexpected_bel), function(i){return(as.vector(HWEexpected_bel[i,]))
})
# Run HWE test
mapply(FUN = chisq.test, x = dat3_bel, p = HWEexpected_bel, SIMPLIFY = FALSE)
[[1]]

    Chi-squared test for given probabilities

data:  dots[[1L]][[1L]]
X-squared = 816.64, df = 2, p-value < 2.2e-16

Belgians are not in HWE ### . Papuans

# convert genotypes and proportions into lists for efficient tests
dat3_pap <- lapply(1:nrow(dat3[4,]), function(i){return(as.vector(dat3[i,]))})
HWEexpected_pap <- lapply(1:nrow(HWEexpected_pap), function(i){return(as.vector(HWEexpected_pap[i,]))
})
# Run HWE test
mapply(FUN = chisq.test, x = dat3_pap, p = HWEexpected_pap, SIMPLIFY = FALSE)
[[1]]

    Chi-squared test for given probabilities

data:  dots[[1L]][[1L]]
X-squared = 10460, df = 2, p-value < 2.2e-16

Papuans are not in HWE

4 . Question 5 Drosophila genotypes

4.1 . Create data frame of observed values

dat <- data.frame(AA = c(100), Aa = c(0), aa = c(100), row.names = c("observed genotype counts"))
dat

4.2 . Calculate allele frequencies to work out expected genotype

proportions (e.g. 1 = p^2+q^2+2pq)
allele_freq_dro <- cbind(((2*dat$AA) + dat$Aa)/(2*rowSums(dat)),
  ((2*dat$aa) + dat$Aa)/(2*rowSums(dat)))
  colnames(allele_freq_dro) <- c("A", "a")
allele_freq_dro
                           A   a
observed genotype counts 0.5 0.5

4.3 . Calculate expected genotype proportions under Hardy-Weinberg Equillibrium

HWEexpected_dro <- t(apply(allele_freq_dro, 1, function(x){
  AA <- x["A"]^2
  Aa <- 2*x["A"]*x["a"]
  aa <- x["a"]^2
  return(cbind(AA, Aa, aa))
  }))
colnames(HWEexpected_dro) <- c("AA", "Aa", "aa")
HWEexpected_dro
                           AA  Aa   aa
observed genotype counts 0.25 0.5 0.25

4.4 . Calculate expected genotype proportions for an F1 generation

AA x aa cross

f1 <- 4 * allele_freq[,1] * allele_freq[,2]
f1
[1] 0.6182825

5 . Question 6 X-linked HWE

5.1 . Calculate allele frequencies to work out expected genotype

proportions (e.g. 1 = p^2+q^2+2pq)
p = 0.08
q = 1-p 
allele_freq <- data.frame("pp" = c(p^2), "2pq" = c(2*p*q), "qq"  = c(q^2), row.names = c("genotype frequency"))
allele_freq

6 . Question 7 Enzyme variation

4 alleles at a locus

6.1 . Create data frame of given frequencies

#A1 = p; A2 = q; A3 = r; A4 = s
allele_freq <- data.frame(p = c(.5), q = c(.3), r = c(.15), s = c(0.05), row.names = c("allele frequencies"))
allele_freq

6.2 . Calculate expected genotype proportions under Hardy-Weinberg Equillibrium

HWEexpected <- t(apply(allele_freq, 1, function(x){
  pp <- x["p"]^2
  pq <- 2*x["p"]*x["q"]
  pr <- 2*x["p"]*x["r"]
  ps <- 2*x["p"]*x["s"]
  qq <- x["q"]^2
  qr <- 2*x["q"]*x["r"]
  qs <- 2*x["q"]*x["s"]
  rr <- x["r"]^2
  rs <- 2*x["r"]*x["s"]
  ss <- x["s"]^2
  
  return(cbind(pp, pq, pr, ps, qq, qr, qs, rr, rs, ss))
  }))
colnames(HWEexpected) <- c("pp", "pq", "pr", "ps", "qq", "qr","qs", "rr", "rs", "ss")
HWEexpected
                     pp  pq   pr   ps   qq   qr   qs     rr    rs     ss
allele frequencies 0.25 0.3 0.15 0.05 0.09 0.09 0.03 0.0225 0.015 0.0025

6.3 . Heterozygote proportion

hetper <- rowSums(HWEexpected) - 
  (HWEexpected[,1] + 
   HWEexpected[,5] +
   HWEexpected[,8] +
   HWEexpected[,10])
hetper
allele frequencies 
             0.635 

6.4 . Specific A4 frequency determination

pop = 100
ss = HWEexpected[,10]
hets <- 2*(HWEexpected[,9]+HWEexpected[,7]+HWEexpected[,4])
print(pophets <- pop*hets)
[1] 19
print(popss <- pop*ss)
[1] 0.25

7 . Question 8 Variance ratio of inbreeding/panmictic

Using the drosophila population frequencies from question 5…

allele_freq_dro <- cbind(((2*dat$AA) + dat$Aa)/(2*rowSums(dat)),
  ((2*dat$aa) + dat$Aa)/(2*rowSums(dat)))
  colnames(allele_freq_dro) <- c("A", "a")
allele_freq_dro
                           A   a
observed genotype counts 0.5 0.5

7.1 . Calculate expected genotype proportions with inbreeding

f = 0.25
HWEexpected_inb <- t(apply(allele_freq_dro, 1, function(x){
  AA <- x["A"]^2 + f*x["A"]*x["a"]
  Aa <- 2*x["A"]*x["a"]*(1-f)
  aa <- x["a"]^2 + f*x["A"]*x["a"]
  return(cbind(AA, Aa, aa))
  }))
colnames(HWEexpected_inb) <- c("AA", "Aa", "aa")
HWEexpected_inb
                             AA    Aa     aa
observed genotype counts 0.3125 0.375 0.3125

7.2 . Compare ratios of HWE and inbreeding

falg = (HWEexpected_dro[,2]-HWEexpected_inb[,2])/HWEexpected_dro[,2]
falg
[1] 0.25
Sys.setenv(RSTUDIO_PANDOC="--- insert directory here ---")
---
title: "R Notebook"
output:
  html_notebook: 
    number_sections: yes
    theme: cerulean
    toc: yes
  pdf_document: default
---
# . Question 1 pgm-1 locus
## . Create data frame of observed values
```{r}
dat <- data.frame(AA = c(634), Aa = c(391), aa = c(85), row.names = c("observed genotype counts"))
dat
```

## . Calculate allele frequencies to work out expected genotype
    proportions (e.g. 1 = p^2+q^2+2pq)
    
```{r}
allele_freq <- cbind(((2*dat$AA) + dat$Aa)/(2*rowSums(dat)),
  ((2*dat$aa) + dat$Aa)/(2*rowSums(dat)))
  colnames(allele_freq) <- c("A", "a")
allele_freq
```

## . Calculate expected genotype proportions under Hardy-Weinberg Equillibrium

```{r}
HWEexpected <- t(apply(allele_freq, 1, function(x){
  AA <- x["A"]^2
  Aa <- 2*x["A"]*x["a"]
  aa <- x["a"]^2
  return(cbind(AA, Aa, aa))
  }))
HWEexpected
```

## . Chisquare test for observed vs expected HWE values
```{r}
# convert genotypes and proportions into lists for efficient tests
dat <- lapply(1:nrow(dat), function(i) return(as.vector(dat[i,])))
HWEexpected <- lapply(1:nrow(HWEexpected), function(i){
return(as.vector(HWEexpected[i,]))
})
# Run HWE test
mapply(FUN = chisq.test, x = dat, p = HWEexpected, SIMPLIFY = FALSE)
```
The p-value is greater than 0.05 so we fail to reject the null hypothesis that the population is in Hardy-Weinberg Equilibrium

# . Question 2 Serum Haptotypes in Egyptians
## . Create data frame of observed values

```{r}
dat2 <- data.frame(pp = c(9), pq = c(135), pr = c(2), qq = c(75),  qr = c(39), rr = c(25), row.names =
                    c("observed genotype counts"))
dat2
```

## . Calculate allele frequencies to work out expected genotype
    proportions (e.g. 1 = p^2+q^2+2pq)
    
```{r}
allele_freq <- cbind(((2*dat2$pp) + dat2$pq + dat2$pr)/(2*rowSums(dat2)),
   ((2*dat2$qq) + dat2$pq + dat2$qr)/(2*rowSums(dat2)),
  ((2*dat2$rr) + dat2$pr + dat2$qr)/(2*rowSums(dat2)))
colnames(allele_freq) <- c("p", "q", "r")
row.names(allele_freq) <- c("gene frequency")
allele_freq
```

## . Calculate expected genotype proportions under Hardy-Weinberg Equillibrium

```{r}
HWEexpected <- t(apply(allele_freq, 1, function(x){
  pp <- x["p"]^2
  pq <- 2*x["p"]*x["q"]
  pr <- 2*x["p"]*x["r"]
  qq <- x["q"]^2
  qr <- 2*x["q"]*x["r"]
  rr <- x["r"]^2
  return(cbind(pp, pq, pr, qq, qr, rr))
  }))
colnames(HWEexpected) <- c("pp", "pq", "pr", "qq", "qr", "rr")
HWEexpected
```

## . Chisquare test for observed vs expected HWE values
```{r}
# convert genotypes and proportions into lists for efficient tests
dat2 <- lapply(1:nrow(dat2), function(i) return(as.vector(dat2[i,])))
HWEexpected <- lapply(1:nrow(HWEexpected), function(i){
return(as.vector(HWEexpected[i,]))
})
# Run HWE test
mapply(FUN = chisq.test, x = dat2, p = HWEexpected, SIMPLIFY = FALSE)
```
p-value is less than 0.05 so we reject the null of HWE. 

# . Question 3 M-N blood groups
## . Create data frame of observed values
```{r}
dat3 <- data.frame(M = c(475, 195, 896, 14), MN = c(89, 215, 1559, 48), N = c(5, 79, 645, 138), row.names = c("Eskimos", "Russians", "Belgians", "Papuans"))
dat3
```

## . Calculate allele frequencies to work out expected genotype
    proportions (e.g. 1 = p^2+q^2+2pq)
### . Eskimos    
```{r}
allele_freq_esk <- cbind(((2*dat3[1,1]) + dat3[1,2])/(2*sum(dat3[1,])),
  ((2*dat3[1,3]) + dat3[1,2])/(2*sum(dat3[1,])))
  colnames(allele_freq_esk) <- c("M", "N")
allele_freq_esk
```
### . Russians
```{r}
allele_freq_rus <- cbind(((2*dat3[2,1]) + dat3[2,2])/(2*sum(dat3[2,])),
  ((2*dat3[2,3]) + dat3[2,2])/(2*sum(dat3[2,])))
  colnames(allele_freq_rus) <- c("M", "N")
allele_freq_rus
```
### . Belgians
```{r}
allele_freq_bel <- cbind(((2*dat3[3,1]) + dat3[3,2])/(2*sum(dat3[3,])),
  ((2*dat3[3,3]) + dat3[3,2])/(2*sum(dat3[3,])))
  colnames(allele_freq_bel) <- c("M", "N")
allele_freq_bel
```
### . Papuans
```{r}
allele_freq_pap <- cbind(((2*dat3[4,1]) + dat3[4,2])/(2*sum(dat3[4,])),
  ((2*dat3[4,3]) + dat3[4,2])/(2*sum(dat3[4,])))
  colnames(allele_freq_pap) <- c("M", "N")
allele_freq_pap
```
## . Calculate expected genotype proportions under Hardy-Weinberg Equillibrium
### . Eskimos
```{r}
HWEexpected_esk <- t(apply(allele_freq_esk, 1, function(x){
  M <- x["M"]^2
  MN <- 2*x["M"]*x["N"]
  N <- x["N"]^2
  return(cbind(M,MN,N))
  }))
colnames(HWEexpected_esk) <- c("M", "MN", "N")
HWEexpected_esk
```
### . Russians
```{r}
HWEexpected_rus <- t(apply(allele_freq_rus, 1, function(x){
  M <- x["M"]^2
  MN <- 2*x["M"]*x["N"]
  N <- x["N"]^2
  return(cbind(M,MN,N))
  }))
colnames(HWEexpected_rus) <- c("M", "MN", "N")
HWEexpected_rus
```
### . Belgians
```{r}
HWEexpected_bel <- t(apply(allele_freq_bel, 1, function(x){
  M <- x["M"]^2
  MN <- 2*x["M"]*x["N"]
  N <- x["N"]^2
  return(cbind(M,MN,N))
  }))
colnames(HWEexpected_bel) <- c("M", "MN", "N")
HWEexpected_bel
```
### . Papuans
```{r}
HWEexpected_pap <- t(apply(allele_freq_pap, 1, function(x){
  M <- x["M"]^2
  MN <- 2*x["M"]*x["N"]
  N <- x["N"]^2
  return(cbind(M,MN,N))
  }))
colnames(HWEexpected_pap) <- c("M", "MN", "N")
HWEexpected_pap
```

## . Chisquare test for observed vs expected HWE values
### . Eskimos
```{r}
# convert genotypes and proportions into lists for efficient tests
dat3_esk <- lapply(1:nrow(dat3[1,]), function(i){return(as.vector(dat3[i,]))})
HWEexpected_esk <- lapply(1:nrow(HWEexpected_esk), function(i){return(as.vector(HWEexpected_esk[i,]))
})
# Run HWE test
mapply(FUN = chisq.test, x = dat3_esk, p = HWEexpected_esk, SIMPLIFY = FALSE)

```
Chi-squared doesn't like low values
#### . Check Eskimo chi-squared against r-package for Hardy-Weinberg
```{r}
library(HardyWeinberg)
eskobs <- c(AA = 475, AB = 89, BB = 5)
HWChisq(eskobs)
```
This test isn't happy either...
To the best that I can tell, Eskimos are in HWE for blood groups
### . Russians
```{r}
# convert genotypes and proportions into lists for efficient tests
dat3_rus <- lapply(1:nrow(dat3[2,]), function(i){return(as.vector(dat3[i,]))})
HWEexpected_rus <- lapply(1:nrow(HWEexpected_rus), function(i){return(as.vector(HWEexpected_rus[i,]))
})
# Run HWE test
mapply(FUN = chisq.test, x = dat3_rus, p = HWEexpected_rus, SIMPLIFY = FALSE)
```
Russians are not in HWE

### . Belgians
```{r}
# convert genotypes and proportions into lists for efficient tests
dat3_bel <- lapply(1:nrow(dat3[3,]), function(i){return(as.vector(dat3[i,]))})
HWEexpected_bel <- lapply(1:nrow(HWEexpected_bel), function(i){return(as.vector(HWEexpected_bel[i,]))
})
# Run HWE test
mapply(FUN = chisq.test, x = dat3_bel, p = HWEexpected_bel, SIMPLIFY = FALSE)
```
Belgians are not in HWE
### . Papuans
```{r}
# convert genotypes and proportions into lists for efficient tests
dat3_pap <- lapply(1:nrow(dat3[4,]), function(i){return(as.vector(dat3[i,]))})
HWEexpected_pap <- lapply(1:nrow(HWEexpected_pap), function(i){return(as.vector(HWEexpected_pap[i,]))
})
# Run HWE test
mapply(FUN = chisq.test, x = dat3_pap, p = HWEexpected_pap, SIMPLIFY = FALSE)
```
Papuans are not in HWE

# . Question 5 Drosophila genotypes

## . Create data frame of observed values
```{r}
dat <- data.frame(AA = c(100), Aa = c(0), aa = c(100), row.names = c("observed genotype counts"))
dat
```

## . Calculate allele frequencies to work out expected genotype
    proportions (e.g. 1 = p^2+q^2+2pq)
    
```{r}
allele_freq_dro <- cbind(((2*dat$AA) + dat$Aa)/(2*rowSums(dat)),
  ((2*dat$aa) + dat$Aa)/(2*rowSums(dat)))
  colnames(allele_freq_dro) <- c("A", "a")
allele_freq_dro
```

## . Calculate expected genotype proportions under Hardy-Weinberg Equillibrium

```{r}
HWEexpected_dro <- t(apply(allele_freq_dro, 1, function(x){
  AA <- x["A"]^2
  Aa <- 2*x["A"]*x["a"]
  aa <- x["a"]^2
  return(cbind(AA, Aa, aa))
  }))
colnames(HWEexpected_dro) <- c("AA", "Aa", "aa")
HWEexpected_dro
```

## . Calculate expected genotype proportions for an F1 generation
AA x aa cross
```{r}
f1 <- 4 * allele_freq[,1] * allele_freq[,2]
f1
```

# . Question 6 X-linked HWE


## . Calculate allele frequencies to work out expected genotype
    proportions (e.g. 1 = p^2+q^2+2pq)
    
```{r}
p = 0.08
q = 1-p 

allele_freq <- data.frame("pp" = c(p^2), "2pq" = c(2*p*q), "qq"  = c(q^2), row.names = c("genotype frequency"))
allele_freq
```

# . Question 7 Enzyme variation
4 alleles at a locus

## . Create data frame of given frequencies

```{r}
#A1 = p; A2 = q; A3 = r; A4 = s
allele_freq <- data.frame(p = c(.5), q = c(.3), r = c(.15), s = c(0.05), row.names = c("allele frequencies"))
allele_freq
```


## . Calculate expected genotype proportions under Hardy-Weinberg Equillibrium

```{r}
HWEexpected <- t(apply(allele_freq, 1, function(x){
  pp <- x["p"]^2
  pq <- 2*x["p"]*x["q"]
  pr <- 2*x["p"]*x["r"]
  ps <- 2*x["p"]*x["s"]
  qq <- x["q"]^2
  qr <- 2*x["q"]*x["r"]
  qs <- 2*x["q"]*x["s"]
  rr <- x["r"]^2
  rs <- 2*x["r"]*x["s"]
  ss <- x["s"]^2
  
  return(cbind(pp, pq, pr, ps, qq, qr, qs, rr, rs, ss))
  }))
colnames(HWEexpected) <- c("pp", "pq", "pr", "ps", "qq", "qr","qs", "rr", "rs", "ss")
HWEexpected
```

## . Heterozygote proportion
```{r}
hetper <- rowSums(HWEexpected) - 
  (HWEexpected[,1] + 
   HWEexpected[,5] +
   HWEexpected[,8] +
   HWEexpected[,10])
hetper
```
## . Specific A4 frequency determination

```{r}
pop = 100
ss = HWEexpected[,10]
hets <- 2*(HWEexpected[,9]+HWEexpected[,7]+HWEexpected[,4])
print(pophets <- pop*hets)
print(popss <- pop*ss)
```

# . Question 8 Variance ratio of inbreeding/panmictic

Using the drosophila population frequencies from question 5...

```{r}
allele_freq_dro <- cbind(((2*dat$AA) + dat$Aa)/(2*rowSums(dat)),
  ((2*dat$aa) + dat$Aa)/(2*rowSums(dat)))
  colnames(allele_freq_dro) <- c("A", "a")
allele_freq_dro
```

## . Calculate expected genotype proportions with inbreeding

```{r}
f = 0.25
HWEexpected_inb <- t(apply(allele_freq_dro, 1, function(x){
  AA <- x["A"]^2 + f*x["A"]*x["a"]
  Aa <- 2*x["A"]*x["a"]*(1-f)
  aa <- x["a"]^2 + f*x["A"]*x["a"]
  return(cbind(AA, Aa, aa))
  }))
colnames(HWEexpected_inb) <- c("AA", "Aa", "aa")
HWEexpected_inb
```
## . Compare ratios of HWE and inbreeding
```{r}
falg = (HWEexpected_dro[,2]-HWEexpected_inb[,2])/HWEexpected_dro[,2]
falg
```
```{r}
Sys.setenv(RSTUDIO_PANDOC="--- insert directory here ---")
```

