annotate shm_overview.htm @ 78:aff3ba86ef7a draft

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author davidvanzessen
date Mon, 31 Aug 2020 11:20:08 -0400
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9 @font-face
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20 font-family:"Calibri","sans-serif";}
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25 line-height:115%;}
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26 @page WordSection1
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27 {size:8.5in 11.0in;
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28 margin:1.0in 1.0in 1.0in 1.0in;}
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29 div.WordSection1
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30 {page:WordSection1;}
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31 -->
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32 </style>
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33
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34 </head>
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35
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36 <body lang=EN-US>
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37
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38 <div class=WordSection1>
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39
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40 <p class=MsoNormalCxSpFirst style='text-align:justify'><b><span lang=EN-GB
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41 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Info
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42 table</span></b></p>
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43
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44 <p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
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45 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>This
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46 table contains information on different characteristics of SHM. For all
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47 characteristics information can be found for all sequences or only sequences of
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48 a certain (sub)class. All results are based on the sequences that passed the filter
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49 settings chosen on the start page of the SHM &amp; CSR pipeline and only
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50 include details on the analysed region as determined by the setting of the
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51 sequence starts at filter. All data in this table can be downloaded via the
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52 “downloads” tab.</span></p>
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53
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54 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
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55 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Mutation
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56 frequency:</span></u></p>
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57
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58 <p class=MsoNormalCxSpMiddle style='text-align:justify'><a name="OLE_LINK83"></a><a
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59 name="OLE_LINK82"></a><a name="OLE_LINK81"><span lang=EN-GB style='font-size:
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60 12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These values
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61 give information on the level of SHM. </span></a><a name="OLE_LINK22"></a><a
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62 name="OLE_LINK21"></a><a name="OLE_LINK20"><span lang=EN-GB style='font-size:
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63 12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>More information
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64 on the values found in healthy individuals of different ages can be found in </span></a><a
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65 name="OLE_LINK15"></a><a name="OLE_LINK14"></a><a name="OLE_LINK13"><span
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66 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>IJspeert
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67 and van Schouwenburg et al, PMID: 27799928</span></a></p>
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68
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69 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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70 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Number
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71 of mutations:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:
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72 115%;font-family:"Times New Roman","serif"'> Shows the number of total
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73 mutations / the number of sequenced bases (the % of mutated bases).</span></p>
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74
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75 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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76 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Median
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77 number of mutations:</span></i><span lang=EN-GB style='font-size:12.0pt;
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78 line-height:115%;font-family:"Times New Roman","serif"'> Shows the median % of
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79 SHM of all sequences.</span></p>
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80
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81 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
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82 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Patterns
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83 of SHM:</span></u></p>
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84
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85 <p class=MsoNormalCxSpMiddle style='text-align:justify'><a name="OLE_LINK72"></a><a
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86 name="OLE_LINK71"></a><a name="OLE_LINK70"><span lang=EN-GB style='font-size:
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87 12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These values
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88 give insights into the targeting and patterns of SHM. These values can give
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89 insight into the repair pathways used to repair the U:G mismatches introduced
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90 by AID. </span></a><a name="OLE_LINK40"></a><a name="OLE_LINK39"></a><a
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91 name="OLE_LINK38"></a><a name="OLE_LINK60"><span lang=EN-GB style='font-size:
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92 12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>More information
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93 on the values found in healthy individuals of different ages can be found in
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94 IJspeert and van Schouwenburg et al, PMID: 27799928</span></a></p>
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95
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96 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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97 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Transitions:</span></i><span
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98 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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99 Shows the number of transition mutations / the number of total mutations (the
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100 percentage of mutations that are transitions). Transition mutations are C&gt;T,
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101 T&gt;C, A&gt;G, G&gt;A. </span></p>
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102
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103 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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104 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Transversions:</span></i><span
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105 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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106 Shows the number of transversion mutations / the number of total mutations (the
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107 percentage of mutations that are transitions). Transversion mutations are
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108 C&gt;A, C&gt;G, T&gt;A, T&gt;G, A&gt;T, A&gt;C, G&gt;T, G&gt;C.</span></p>
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109
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110 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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111 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Transitions
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112 at GC:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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113 font-family:"Times New Roman","serif"'> <a name="OLE_LINK2"></a><a
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114 name="OLE_LINK1">Shows the number of transitions at GC locations (C&gt;T,
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115 G&gt;A) / the total number of mutations at GC locations (the percentage of
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116 mutations at GC locations that are transitions).</a></span></p>
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117
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118 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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119 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Targeting
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120 of GC:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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121 font-family:"Times New Roman","serif"'> <a name="OLE_LINK7"></a><a
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122 name="OLE_LINK6"></a><a name="OLE_LINK3">Shows the number of mutations at GC
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123 locations / the total number of mutations (the percentage of total mutations
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124 that are at GC locations).</a> </span></p>
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125
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126 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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127 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Transitions
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128 at AT:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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129 font-family:"Times New Roman","serif"'> Shows the number of transitions at AT
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130 locations (T&gt;C, A&gt;G) / the total number of mutations at AT locations (the
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131 percentage of mutations at AT locations that are transitions).</span></p>
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132
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133 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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134 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Targeting
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135 of AT:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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136 font-family:"Times New Roman","serif"'> Shows the number of mutations at AT
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137 locations / the total number of mutations (the percentage of total mutations
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138 that are at AT locations).</span></p>
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139
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140 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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141 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>RGYW:</span></i><span
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142 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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143 <a name="OLE_LINK28"></a><a name="OLE_LINK27"></a><a name="OLE_LINK26">Shows
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144 the number of mutations that are in a RGYW motive / The number of total mutations
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145 (the percentage of mutations that are in a RGYW motive). </a><a
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146 name="OLE_LINK62"></a><a name="OLE_LINK61">RGYW motives are known to be
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147 preferentially targeted by AID </a></span><span lang=EN-GB style='font-size:
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148 12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(R=Purine,
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149 Y=pyrimidine, W = A or T).</span></p>
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150
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151 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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152 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>WRCY:</span></i><span
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153 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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154 <a name="OLE_LINK34"></a><a name="OLE_LINK33">Shows the number of mutations
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155 that are in a </a><a name="OLE_LINK32"></a><a name="OLE_LINK31"></a><a
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156 name="OLE_LINK30"></a><a name="OLE_LINK29">WRCY</a> motive / The number of
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157 total mutations (the percentage of mutations that are in a WRCY motive). WRCY
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158 motives are known to be preferentially targeted by AID </span><span lang=EN-GB
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159 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(R=Purine,
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160 Y=pyrimidine, W = A or T).</span></p>
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161
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162 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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163 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>WA:</span></i><span
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164 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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165 <a name="OLE_LINK37"></a><a name="OLE_LINK36"></a><a name="OLE_LINK35">Shows
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davidvanzessen
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166 the number of mutations that are in a WA motive / The number of total mutations
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davidvanzessen
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167 (the percentage of mutations that are in a WA motive). It is described that
ba33b94637ca Uploaded
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168 polymerase eta preferentially makes errors at WA motives </a></span><span
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169 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(W
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170 = A or T).</span></p>
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davidvanzessen
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171
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172 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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173 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>TW:</span></i><span
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174 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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175 Shows the number of mutations that are in a TW motive / The number of total mutations
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davidvanzessen
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176 (the percentage of mutations that are in a TW motive). It is described that
ba33b94637ca Uploaded
davidvanzessen
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177 polymerase eta preferentially makes errors at TW motives </span><span
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178 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(W
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179 = A or T).</span></p>
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davidvanzessen
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180
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181 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
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182 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Antigen
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183 selection:</span></u></p>
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184
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185 <p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
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186 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These
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187 values give insight into antigen selection. It has been described that during
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davidvanzessen
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188 antigen selection, there is selection against replacement mutations in the FR
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davidvanzessen
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189 regions as these can cause instability of the B-cell receptor. In contrast
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davidvanzessen
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190 replacement mutations in the CDR regions are important for changing the
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davidvanzessen
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191 affinity of the B-cell receptor and therefore there is selection for this type
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davidvanzessen
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192 of mutations. Silent mutations do not alter the amino acid sequence and
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davidvanzessen
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193 therefore do not play a role in selection. More information on the values found
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davidvanzessen
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194 in healthy individuals of different ages can be found in IJspeert and van
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davidvanzessen
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195 Schouwenburg et al, PMID: 27799928</span></p>
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196
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197 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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198 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>FR
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199 R/S:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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davidvanzessen
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200 font-family:"Times New Roman","serif"'> <a name="OLE_LINK43"></a><a
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davidvanzessen
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201 name="OLE_LINK42"></a><a name="OLE_LINK41">Shows the number of replacement
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davidvanzessen
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202 mutations in the FR regions / The number of silent mutations in the FR regions
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davidvanzessen
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203 (the number of replacement mutations in the FR regions divided by the number of
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davidvanzessen
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204 silent mutations in the FR regions)</a></span></p>
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davidvanzessen
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205
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davidvanzessen
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206 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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207 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>CDR
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208 R/S:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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davidvanzessen
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209 font-family:"Times New Roman","serif"'> Shows the number of replacement
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davidvanzessen
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210 mutations in the CDR regions / The number of silent mutations in the CDR
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davidvanzessen
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211 regions (the number of replacement mutations in the CDR regions divided by the
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davidvanzessen
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212 number of silent mutations in the CDR regions)</span></p>
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davidvanzessen
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213
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davidvanzessen
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214 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
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215 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Number
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216 of sequences nucleotides:</span></u></p>
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davidvanzessen
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217
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218 <p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
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219 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These
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davidvanzessen
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220 values give information on the number of sequenced nucleotides.</span></p>
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davidvanzessen
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221
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davidvanzessen
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222 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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223 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Nt
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davidvanzessen
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224 in FR:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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davidvanzessen
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225 font-family:"Times New Roman","serif"'> <a name="OLE_LINK46"></a><a
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davidvanzessen
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226 name="OLE_LINK45"></a><a name="OLE_LINK44">Shows the number of sequences bases
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davidvanzessen
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227 that are located in the FR regions / The total number of sequenced bases (the
ba33b94637ca Uploaded
davidvanzessen
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228 percentage of sequenced bases that are present in the FR regions).</a></span></p>
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davidvanzessen
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229
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davidvanzessen
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230 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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231 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Nt
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davidvanzessen
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232 in CDR:</span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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davidvanzessen
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233 font-family:"Times New Roman","serif"'> Shows the number of sequenced bases
ba33b94637ca Uploaded
davidvanzessen
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234 that are located in the CDR regions / <a name="OLE_LINK48"></a><a
ba33b94637ca Uploaded
davidvanzessen
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235 name="OLE_LINK47">The total number of sequenced bases (the percentage of
ba33b94637ca Uploaded
davidvanzessen
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236 sequenced bases that are present in the CDR regions).</a></span></p>
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davidvanzessen
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237
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davidvanzessen
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238 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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davidvanzessen
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239 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>A:
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davidvanzessen
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240 </span></i><a name="OLE_LINK51"></a><a name="OLE_LINK50"></a><a
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davidvanzessen
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241 name="OLE_LINK49"><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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davidvanzessen
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242 font-family:"Times New Roman","serif"'>Shows the total number of sequenced
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davidvanzessen
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243 adenines / The total number of sequenced bases (the percentage of sequenced
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davidvanzessen
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244 bases that were adenines).</span></a></p>
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davidvanzessen
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245
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davidvanzessen
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246 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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davidvanzessen
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247 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>C:
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davidvanzessen
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248 </span></i><a name="OLE_LINK53"></a><a name="OLE_LINK52"><span lang=EN-GB
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davidvanzessen
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249 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Shows
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davidvanzessen
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250 the total number of sequenced cytosines / The total number of sequenced bases
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davidvanzessen
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251 (the percentage of sequenced bases that were cytosines).</span></a></p>
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davidvanzessen
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252
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davidvanzessen
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253 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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davidvanzessen
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254 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>T:
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davidvanzessen
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255 </span></i><a name="OLE_LINK57"></a><a name="OLE_LINK56"><span lang=EN-GB
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davidvanzessen
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256 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Shows
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davidvanzessen
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257 the total number of sequenced </span></a><a name="OLE_LINK55"></a><a
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davidvanzessen
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258 name="OLE_LINK54"><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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259 font-family:"Times New Roman","serif"'>thymines</span></a><span lang=EN-GB
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260 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>
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davidvanzessen
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261 / The total number of sequenced bases (the percentage of sequenced bases that
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davidvanzessen
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262 were thymines).</span></p>
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davidvanzessen
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263
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davidvanzessen
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264 <p class=MsoNormalCxSpMiddle style='text-align:justify'><i><span lang=EN-GB
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davidvanzessen
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265 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>G:
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davidvanzessen
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266 </span></i><span lang=EN-GB style='font-size:12.0pt;line-height:115%;
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davidvanzessen
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267 font-family:"Times New Roman","serif"'>Shows the total number of sequenced <a
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davidvanzessen
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268 name="OLE_LINK59"></a><a name="OLE_LINK58">guanine</a>s / The total number of
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davidvanzessen
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269 sequenced bases (the percentage of sequenced bases that were guanines).</span></p>
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davidvanzessen
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270
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davidvanzessen
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271 <p class=MsoNormalCxSpMiddle style='text-align:justify'><a name="OLE_LINK69"><b><span
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272 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Graphs</span></b></a></p>
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273
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davidvanzessen
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274 <p class=MsoNormalCxSpMiddle style='text-align:justify'><a name="OLE_LINK75"></a><a
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davidvanzessen
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275 name="OLE_LINK74"></a><a name="OLE_LINK73"><span lang=EN-GB style='font-size:
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davidvanzessen
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276 12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>These graphs visualize
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davidvanzessen
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277 information on the patterns and targeting of SHM and thereby give information
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davidvanzessen
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278 into the repair pathways used to repair the U:G mismatches introduced by AID. The
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davidvanzessen
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279 data represented in these graphs can be downloaded in the download tab. More
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davidvanzessen
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280 information on the values found in healthy individuals of different ages can be
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davidvanzessen
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281 found in IJspeert and van Schouwenburg et al, PMID: 27799928</span></a><span
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282 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>.
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davidvanzessen
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283 <a name="OLE_LINK85"></a><a name="OLE_LINK84"></a></span></p>
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davidvanzessen
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284
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davidvanzessen
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285 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=EN-GB
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286 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Percentage
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287 of mutations in AID and pol eta motives</span></u></p>
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davidvanzessen
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288
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davidvanzessen
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289 <p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
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davidvanzessen
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290 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Visualizes
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davidvanzessen
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291 <a name="OLE_LINK80"></a><a name="OLE_LINK79"></a><a name="OLE_LINK78">for each
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davidvanzessen
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292 (sub)class </a>the percentage of mutations that are present in AID (RGYW or
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davidvanzessen
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293 WRCY) or polymerase eta motives (WA or TW) in the different subclasses </span><span
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davidvanzessen
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294 lang=EN-GB style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>(R=Purine,
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295 Y=pyrimidine, W = A or T).</span></p>
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davidvanzessen
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296
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davidvanzessen
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297 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=NL
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298 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Relative
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299 mutation patterns</span></u></p>
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davidvanzessen
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300
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301 <p class=MsoNormalCxSpMiddle style='text-align:justify'><span lang=EN-GB
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davidvanzessen
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302 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Visualizes
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davidvanzessen
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303 for each (sub)class the distribution of mutations between mutations at AT
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davidvanzessen
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304 locations and transitions or transversions at GC locations. </span></p>
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davidvanzessen
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305
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davidvanzessen
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306 <p class=MsoNormalCxSpMiddle style='text-align:justify'><u><span lang=NL
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307 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Absolute
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308 mutation patterns</span></u></p>
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davidvanzessen
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309
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davidvanzessen
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310 <p class=MsoNormalCxSpLast style='text-align:justify'><span lang=EN-GB
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davidvanzessen
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311 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Visualized
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davidvanzessen
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312 for each (sub)class the percentage of sequenced AT and GC bases that are
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davidvanzessen
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313 mutated. The mutations at GC bases are divided into transition and transversion
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davidvanzessen
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314 mutations<a name="OLE_LINK77"></a><a name="OLE_LINK76">. </a></span></p>
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davidvanzessen
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315
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davidvanzessen
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316 <p class=MsoNormal><span lang=NL style='font-size:12.0pt;line-height:115%;
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317 font-family:"Times New Roman","serif"'>Hanna IJspeert, Pauline A. van
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318 Schouwenburg, David van Zessen, Ingrid Pico-Knijnenburg, Gertjan J. Driessen,
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319 Andrew P. Stubbs, and Mirjam van der Burg (2016). </span><span
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320 style='font-size:12.0pt;line-height:115%;font-family:"Times New Roman","serif"'>Evaluation
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321 of the Antigen-Experienced B-Cell Receptor Repertoire in Healthy Children and
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322 Adults. In <i>Frontiers in Immunolog, 7, pp. e410-410. </i>[<a
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323 href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066086/"><span
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324 style='color:windowtext'>doi:10.3389/fimmu.2016.00410</span></a>][<a
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325 href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066086/"><span
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326 style='color:windowtext'>Link</span></a>]</span></p>
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327
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328 </div>
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329
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330 </body>
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331
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332 </html>