Kinship tutorial

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Kinship tutorial
B
Y
A

• Using the DNAVIEW Kinship program(s)
• Charles Brenner, PhD
• http//dna-view.com

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Kinship introduction

• Two symbolic kinship programs
• prototype Kinship program (1993)
• stand-alone manually enter genotypes
  frequencies locus-by-locus operation
• both in DNAVIEW and in PATER
• Immigration-Kinship (Sep 1998)
• integrated, automatic operation
• DNAVIEW only (under Case commands)
• includes Kinship Simulation (June 2002)

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Drawing pedigree diagrams

• Input to Kinship includes pedigree information
  (description of relationships).
• Begin by drawing pedigree diagrams.
• Ex

female
ok style
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Pedigree diagram
Albon
Sylvie
Y
A

• Name each person
• single letter for typed people (Y, A)
• capitalize names (Y, Albon, not y, albon)
• Multiple (disjoint) trees ok

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Pedigree diagram

• Include common ancestors

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Kinship notation

• Child Mom Dad

• Child Mom Dad

Y Sylvie Albon A Sylvie Albon
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Kinship notation
?
Y Sylvie Albon A Sylvie Albon Sylvie
Ellie Aden B Ellie Aden

• For each child, say who the parents are. That
  exactly describes the picture.

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Creating kinship hypotheses

• Draw a pedigree diagram
• introduce additional names as necessary
• Transcribe into Kinship notation underneath
• Example C is the child of M and F

C M F
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Kinship hypothesis exercise

• Example C is the nephew of U

U Gma Gpa C Ma Pa Pa Gma Gpa
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Kinship half-sibling exercise

• Example A and Z are half-siblings (same father).
  As mother is typed.

A M Max Z ZMa Max
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Review quiz Whats wrong?

• Cs parents are m and Joe
• C m Joe whats wrong?
• M, not m. Names begin with capitals.
• Pats mother is M whose mother is W
• Pat (M WGpa) Pa whats wrong?
• Need 2 statements no parentheses
• Js mother is M
• J M whats wrong?
• Need 2 parents

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Kinship incest exercise

• Example Baby and Mother have the same father.
  Baby, Mother, and Mothers brother are typed.

U Gma Fa M Gma Fa B M Fa
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Review quiz Whats wrong?

• Q and Audrey are half-siblings
• Q Pat Joe
• Audrey M Pat
• whats wrong?
• Pat is both a mother and a father

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Solving Kinship Problems

• The value of Kinship lies in comparing two
  hypotheses.
• Which explains the genetic (DNA) data better?
  (and by how much?)
• Example the paternity problem
• M and F are the parents of C
• vs
• M is the mother of C, F is unrelated.

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Kinship likelihood ratio (LR)

• Example the paternity problem
• M and F are the parents of C vs
• M is the mother of C, F is unrelated.
• Kinship result is the LR
• P(DNA data Ffather) / P(DNA data
  Funrelated)
• In general, Kinship computes LRX/Y where
• X P(DNA data principle hypothesis)
• Y P(DNA data alternative hypothesis)

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Kinship Symbolic LR

• Kinship first derives the LR algebraically
• p, q, r, probabilities of alleles p, q, r
• then estimates allele probabilities from
  appropriate population databases
• probability formula per various user options
• e.g. if sample frequency for q is k/n, usually
  q(k1)/(n1)

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Comparing kinship hypotheses

• Draw the two pedigree diagrams on left and right
  sides of the paper
• Transcribe each into Kinship notation underneath
• Example C is the child of M and F, vs only of M

C M F
C M Guy
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Practicing on the computer overview

• That covers the principles of defining a kinship
  problem.
• Before proceeding with more interesting and
  difficult exercises, it will be useful to discuss
  the entire routine of running kinship cases in
  DNAVIEW
• so that you can integrate the theory with practice

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Solving a Kinship problem overview

• Create a tab-delimited text file with all the
  data
• the DNA profiles
• identified with people (role letters) in a case
  (number)
• Import it (Import/export Genotyper import)
• Use the Immigration/Kinship facility to solve the
  problem
• result file automatically created
• results shown on screen, and printable log file
  available

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Practice data file

• KinPPT.xls
• possibly found as
• C dnaview examples KinPPT.xls
• contains DNA profiles and Case definitions for
  the practice cases 1217-1221 discussed in this
  Powerpoint as an Excel table.

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Creating a Kinship data file

• Create a table like the above (Excel or
  Genotyper?)
• 1217case. M, F, Crole letters. Momcomment
• Multiple cases ok, or a case may be split across
  multiple tables.
• Many variations permitted see the manual.
• Save as
• Save as type text (tab delimited)
• Save in C dnaview import
• File name KinPPT.txt
• (or use examples\kinPPT.gen)

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Importing a Kinship data file 1

• Assume a tab-delimited text file of DNA profiles
  labeled with case-and-role information
• Import it (Import/export Genotyper import)

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Importing a Kinship data file 2
type the subdirectory (folder) examples
enter choose the file from the menu KinPPT.gen
enter

• End, then Enter four times, to create a new,
  empty membrane (worklist) with 099 as reader
  (analyst)

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Importing a Kinship data file 3

• End to approve the locus interpretation chart

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Importing a Kinship data file 4

• n
• Kin enter
• c enter
• enter

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Importing a Kinship data file 5

• enter

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Importing a Kinship data file 6

• Cases 1217-1221 have been created.
• DNA profiles for the people in them are saved.
• Esc twice to return to the main menu.

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Solving Kinship problems with DNAVIEW

• For now, we use the automatic, Immigration-Kinship
  , version.
• Assume that a Case has been defined and relevant
  DNA data has been entered into the program
• (Easiest method Genotyper import does both from
  a tab-delimited text spreadsheet.)
• The Case includes people with roles C, M etc
  the names used for typed people.
• Invoke Casework Automatic Kinship select case
  (type the case 1217) Immigration/Kinship

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Entering kinship hypotheses into the computer

• Select the Kinship menu item Type in scenario.
• The two hypotheses are principal and alternate.
• / indicates the alternate hypothesis.
• Type in all statements of both hypotheses.
• Prefix each alternate hypothesis statement with /.

C M F / C M Guy

• Hit Esc to return to the Kinship menu.

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Compute! (case 1217)

• Select the Kinship menu item Calculate report
  LRs, x races (calculation occurs accept filing
  suggestion)
• Select Show summary

D3S1358 4.28 1 / p
p0.233 VWA 1.02 1 / (2s2t)
s0.265 t0.224 FGA 6.78 1 / p
p0.148 D8S1179 24.6 1 /
2p p0.0204 D21S11 2.98 1
/ 2p p0.168 D18S51 3.28
1 / (pr) p0.13 r0.176 D5S818
3.37 1 / 2r r0.148 D13S317
1.61 1 / 2t t0.31 D7S820
3.42 1 / p p0.292 cumulative LR
132000
C M F / C M Guy

• Hit Esc to return to the Kinship menu.

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End of case 1217

• Analyze other scenarios if desired. (None)
• Esc to exit from the Immigration/kinship menu
  back to the Automatic Kinship Case menu
• Switch to Windows (Alt-tab, or perhaps
  Alt-Enter), and examine the kinship report
  C\dnaview\reports\k1217.txt if desired.
• Switch to DNAVIEW (Alt-tab)
• Choose select case to prepare for the next
  exercise

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Body ID exercise (Case 1218)

• Reference profiles are available Sylvies brother
  B and her son A. The father of A is Albon.
• Does the DNA from the body fragment Y represent a
  brother of A?

Y Sylvie Albon A Sylvie Albon Sylvie
Ellie Aden B Ellie Aden
/ A Sylvie Albon / Sylvie Ellie Aden / B
Ellie Aden
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Avuncular exercise (Case 1219)

• Are C and U nephew and uncle, or are they
  unrelated?

C Ma Pa Pa Gma Gpa U Gma Gpa
/ C Ma Pa
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Avuncular exercise comment

• Alternative C and U unrelated
• Us parents are irrelevant, so ? shows a
  sufficient alternative.
• Cs parents are also irrelevant, so really no
  alternative scenario statements are necessary at
  all. ?
• In fact (shortcut) the empty alternative may be
  omitted altogether. ?

C Ma Pa Pa Gma Gpa U Gma Gpa / C
MPa
C Ma Pa Pa Gma Gpa U Gma Gpa /
C Ma Pa Pa Gma Gpa U Gma Gpa
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Half-sibling exercise (Case 1220)

• Are Z and A half-siblings, or are they unrelated?

A M Max Z ZMa Max
/ A M Max
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Incest exercise (Case 1221)

• Is Ms baby B from her (untyped) father, or from
  her (typed) brother U?

M Gma Fa U Gma Fa B M Fa
/ M Gma Fa / U Gma Fa / B M U
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Compute case 1221
Summary of calculation
Scenario
D3S1358 500 1 / µ
µ1/500 q0.248 r0.233 VWA 333
1 / µ µ1/333 s0.265 FGA
0.66 (14p3pp) / (24p2pp)
p0.191 D8S1179 0.77
(1p4u5puuu) / (22p2u4pu) p0.0127
u0.204 D21S11 0.5 1 / 2 D18S51
1.23 (2p7r) / (24r)
p0.13 r0.158 D5S818 0.646 (12p) /
(22p) p0.412 D13S317
0.867 (25p5qpp10pqqq) / p0.321
q0.31
(44p4q8pq) D7S820 0.695
(25p5tpp10pttt) / p0.292
t0.0123
(44p4t8pt) D16S539 1.39 (2p7q)
/ (24q) p0.274 q0.341 TH01
0.875 (3a5p) / (44p)
p0.128 a0.307 TPOX 0.561
(12ps) / (24p) p0.545
s0.256 CSF1PO 0.614 (1pq) /
(22q) p0.302 q0.327 cumulative
LR 8460
D3S1358 500 1 / µ
µ1/500 q0.248 r0.233 VWA 333
1 / µ µ1/333 s0.265
M Gma Fa U Gma Fa B M Fa / M
Gma Fa / U Gma Fa / B M U

• Evidence, favoring Fa over U, is concentrated in
  D3S1358 and VWA.

• Note 1/?, ?mutation rate

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Wherefore mutation?

• Examine the genotypes (Estimate likely
  relationships). Assuming Ufather of B,
  observed data requires mutations

• D3S1358 p14 q15 r16 s17
• VWA p14 q15 s17 t18

• D3 1 step p?q or s?r
• vWA 2 step q ?s (15 ?17)
• (Alphabetical distance does reflect STR repeat
  difference.)
• Kinships 1/? is simplification, requires manual
  review
• In D3, overestimates 1/(?/4q?/4r) ? 1/2?
  (because 2 possibilities)
• In vWA, underestimates 40s/? ? 10/? (because
  2-step mutation)
• Net Adjust LR to 8460(1/2)(10) ? 40,000.

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Missing body quiz whats wrong?

• Missing body problem
• Body V may be Sam, the son of G and the father of
  D.
• I typed into Kinship
• What did I do wrong?

V G Raphael D Xyz V /
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Missing body quiz answer
V G Raphael D Xyz V /

• says that either
• V, G, D are related, or
• none of them are related
• (ignores grandmother-granddaughter relationship
  between G and D)

• correct is

V G Raphael D Xyz V / Sam G
Raphael / D Xyz Sam
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Missing body point of nomenclature
V G Raphael D Xyz V / Sam G
Raphael / D Xyz Sam

• V refers to the dead body, which may or may not
  be Sam.
• Under the principle hypothesis, V is attached to
  the DNA profile of Sam.
• Use the name V to link the references.
• Under the alternative hypothesis, V is related to
  no one.
• Use the name Sam to link the references.

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Helpful pointers about typing scenarios

• Do spaces matter?
• Can I copy and paste?
• Can I recall or save scenarios?
• Any other tricks?

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Do spaces matter?

• No. Put them where you wish for appearance
• D AuntSallyRoger
• E M D
• (except please dont put a space in the middle of
  a name)
• D Aunt Sally Roger
• No!

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Can I copy and paste?

• To capture a rectangular area
• Single left click at one corner to position the
  typing mark (the small rectangle that moves when
  you type).
• Float (dont click yet!) the mouse arrow at the
  opposite corner.
• Right click to select and copy.
• To paste
• Left click to mark the upper left corner of the
  destination.
• Ctrl-v to paste a captured rectangle per above

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Can I copy and paste from Windows?

• Select and copy from a Windows document.
• To paste
• Left click to mark the upper left corner of the
  destination in DNAVIEWs scenario window.
• Right click on the DNAVIEW title bar
• Slide from Edit, then click on Paste

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Can I recall or save scenarios?

• Permanently
• Add to pick list menu item saves current
  scenario.
• Pick it (from the bottom of the immigration menu)
  to retrieve it.
• Temporarily (per F1 help menu)
• Current scenario is saved every time you Esc from
  the scenario type-in window.
• PageUp / PageDown recall previous scenarios.
• Ctrl-UpArrow for menu of previous scenarios.

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Any other tricks?

• When typing a scenario F1 pops up help, e.g.
• Ctrl-z undoes recent typing
• Esc then Type in scenario to commit input so far.
• Ctrl-Ins and Ctrl-Del insert or remove a line
• Multiple statements on a line
• Separate with or with ? (alt-) or (alt-sh-8)
• CMU ? DMU

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Suggestions for further study

• See the Kinship chapter
• additional notation
• for comments
• , for full siblings
• ? for a computer-generated name
• concise alternative input style
• embed the / instead of prefixing it
• Mutation http//dna-view.com/mudisc.htm
• Comparing 3 or more hypotheses
• http//dna-view.com/manyhyp.htm
• Kinship simulation

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The end