Tokutomi et al. BMC Medical Genetics (2017) 18:71
DOI 10.1186/s12881-017-0433-4

SOFTWARE

Open Accessf-treeGC: a questionnaire-based family treecreation software for genetic counselingand genome cohort studies
Tomoharu Tokutomi1,2, Akimune Fukushima1,2* , Kayono Yamamoto1,2, Yasushi Bansho3, Tsuyoshi Hachiya4
and Atsushi Shimizu4

Abstract
Background: The Tohoku Medical Megabank project aims to create a next-generation personalized healthcare system
by conducting large-scale genome-cohort studies involving three generations of local residents in the areas affected by
the Great East Japan Earthquake. We collected medical and genomic information for developing a biobank to be used forthis healthcare system. We designed a questionnaire-based pedigree-creation software program named “f-treeGC,” whichenables even less experienced medical practitioners to accurately and rapidly collect family health history and create
pedigree charts.
Results: f-treeGC may be run on Adobe AIR. Pedigree charts are created in the following manner: 1) At system startup,
the client is prompted to provide required information on the presence or absence of children; f-treeGC is capable ofcreating a pedigree up to three generations. 2) An interviewer fills out a multiple-choice questionnaire on genealogicalinformation. 3) The information requested includes name, age, gender, general status, infertility status, pregnancy status,
fetal status, and physical features or health conditions of individuals over three generations. In addition, information
regarding the client and the proband, and birth order information, including multiple gestation, custody,
multiple individuals, donor or surrogate, adoption, and consanguinity may be included. 4) f-treeGC shows
only marriages between first cousins via the overlay function. 5) f-treeGC automatically creates a pedigree
chart, and the chart-creation process is visible for inspection on the screen in real time. 6) The genealogical data may
be saved as a file in the original format. The created/modified date and time may be changed as required, and the file
may be password-protected and/or saved in read-only format. To enable sorting or searching from the database, thefile name automatically contains the terms typed into the entry fields, including physical features or health conditions,by default. 7) Alternatively, family histories are collected using a completed foldable interview paper sheet
named “f-sheet”, which is identical to the questionnaire in f-treeGC.
Conclusions: We developed a questionnaire-based family tree-creation software, named f-treeGC, which is
fully compliant with international recommendations for standardized human pedigree nomenclature. The
present software simplifies the process of collecting family histories and pedigrees, and has a variety ofuses, from genome cohort studies or primary care to genetic counseling.
Keywords: Pedigree, Family tree, Software, Questionnaire, Family health history, Interview sheet, Genetic
counseling, Genome cohort studies, Primary care, Biobank* Correspondence: akimunef@iwate-med.ac.jp
1
Department of Clinical Genetics, School of Medicine, Iwate Medical
University, Morioka, Iwate 020-8505, Japan
2
Division of Innovation and Education, Iwate Tohoku Medical Megabank
Organization, Iwate Medical University, Shiwa, Iwate 028-3694, Japan
Full list of author information is available at the end of the article© The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Tokutomi et al. BMC Medical Genetics (2017) 18:71

Background
Genealogical information is critical for accurate genetic
diagnosis in clinical genetics. In 1995, the National Societyof Genetic Counselors [1] introduced a standardized description method for presenting a family tree in genetic
counseling, which was revised in 2008 to the current version [2]. Typically, pedigree charts are manually created
via face-to-face personal interviews held on an individual
basis. However, pedigree chart creation requires graphicalskills and specialized knowledge of clinical genetics, and isthus a time- and labor-intensive process. A large amountof genetic data has been collected from numerous largescale studies conducted in recent years, such as genomecohort studies. The availability of accurate genealogicalinformation is essential for performing comprehensive
analysis of polymorphisms and associated diseases for use
in genetic counseling, research, and diagnosis. Given thelarge amount of genetic information required and collected, it is currently not possible to create pedigree charts
using the traditional method through interviews at a single
recruiting event by an expert.
The Tohoku Medical Megabank (TMM) project [3]aims to restore community medical services that were
negatively affected by the Great East Japan Earthquake,and to create a next-generation personalized healthcare
system by conducting large-scale genome-cohort studies
involving three generations of local residents in thedisaster-stricken areas [4]. Specifically, we collected
medical and genomic information, including family
health history, for developing a biobank to be used in
the planned healthcare system.
In this project, we designed a questionnaire-based
pedigree-drawing software program named “f-treeGC”,
which enables even less-experienced medical practitioners to accurately and rapidly collect genealogical information and create pedigree charts, in full compliancewith international standards [2].
Implementation
Programming

f-treeGC is written in ActionScript 3.0, and may be run
on Adobe AIR, which is a cross-platform runtime system.
Operating environment

f-treeGC is supported by both Windows (Windows 7, 8,
and 10) and Macintosh (operating system (OS) X).
Adobe AIR Runtime [5] must be installed before installation and use of f-treeGC, and Adobe Reader DC [6] isrequired for the printing function. Via these programs,
the f-treeGC air file may be opened to install the software. The f-treeGC software program is available foruse, at no monetary cost, at the Iwate Medical University
Hospital website (http://www.iwate-med.ac.jp/hospital/
clinics/medical/m26/).

Page 2 of 12

Results
The method for the creation of pedigree charts is
described in the following sections.

Confirmation of whether or not the client has a childAt system startup, the client is prompted to provide required information on the presence or absence of children (Additional file 1a). f-treeGC is capable of creatinga pedigree that includes three generations (Fig. 1a). Couples with offspring are included in the 2nd generation of
the family tree (Fig. 2a, Additional file 2), whereas clientswith no children are included in the 3rd generation(Figs. 1a and 2b, Additional file 3). A representative correspondence table is shown in Table 1.

Multiple-choice questionnaire

The genealogical information requested includes name,age, gender, general status (affected, asymptomatic/presymptomatic carrier, carrier, or deceased), infertility
status, pregnancy status, fetal status, and health status(occurrence of any diseases) of individuals in the three
generations. In addition, information regarding clientand proband, as well as birth order information such as
multiple gestation, custody, multiple individuals, donoror surrogate, adoption, and consanguinity may be included (Fig. 1).
By default, the “Name” field refers to the type of relationship such as father or mother. The user should
delete the relationship name before inputting the relevant name (Fig. 1b). In the “Age” box (Fig. 1c) and the“Gestational age (weeks)” box (Fig. 1d), the user may
select “In blank”, “? (unknown)”, or the relevant number. Inputting the same number of individuals in the“Multiple-gestation ID” (Fig. 1e) indicates multiple
gestation or pregnancy with multiple fetuses. The“Monozygotic” box (Fig. 1f ) is for identical twins(pregnancy). The “Custody” box (Fig. 1g) is for the
position of a break in a relationship line between divorced partners, and indicates the parent(s) with primary responsibility for the children following divorce.
For multiple individuals, users may select “n (unknown)” or the relevant number(s) after checking the“Multiple individuals” box (Fig. 1h). The “Affected”
button of general status (Fig. 1i) is for affected individuals, and users may set a key color for the affected
status in the configuration (Fig. 1j). For affected individuals with two or more conditions, the user may
check for the conditions (Fig. 1k). Considering the diversity in color perception and to enable distinction insubsequent black-and-white photocopies, f-treeGC
shows multiple conditions using a color of a similar
shade (Additional file 1b).

Tokutomi et al. BMC Medical Genetics (2017) 18:71

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Fig. 1 Information entry screen of f-treeGC; information for three generations is required to create the pedigree (a). The genealogicalinformation requested includes name (b, u), age (c, d), gender, general status [affected (i, j, k), asymptomatic/presymptomatic carrier,
carrier, or deceased], infertility status, pregnancy status, fetal status, and disease status (m, n, o, p, q, t) of individuals belonging tothree generations. In addition, client, proband and birth order information, including multiple gestation (e, f), custody (g), multiple individuals (h), donoror surrogate, adoption, and consanguinity (l) information may be inserted. The chart-creation process is visible for inspection on the lower left side of
the f-treeGC screen in real time (r). A multiple-choice questionnaire for genetic information is filled out by an interviewer or the client; then, f-treeGC
automatically creates a pedigree chart (r, s, t, v, w)

A printed paper version of the questionnaire

Alternatively, family health histories may be collectedusing the foldable interview sheet named “f-sheet”(Fig. 3, Additional file 4), which is a printed paper
version of the questionnaire in f-treeGC. The f-sheet
provides an overview of genetic relationships between
families according to the manner in which the sheet
is folded or developed. For example, the vertical lineof the folded f-sheet corresponds to the left panel ofthe f-treeGC (Fig. 1a). Filling out a multiple-choicequestionnaire on genetic information is easier for a
medical practitioner with poor digital literacy. A
skilled data entry clerk may subsequently input family
health histories into f-treeGC from the f-sheet as abundle.

Overlay function for consanguinity

With respect to consanguinity, f-treeGC shows only
marriages between first cousins using the overlay function. The “Consanguinity” box should be checked andthe same “Overlay ID” should be entered for this function to be effective (Figs. 1l and 4, Additional file 5).
Entry fields and keys for physical features or diseases/
conditions for genome cohort studies

By default, the file name automatically contains the firstten letters (Fig. 1m) that are typed into the sixteen entry
fields of the “Disease, etc./KEY,” such as disease name(Fig. 1n), and for which the box is checked (Fig. 1o), toenable sorting or searching from the database. For example, the preliminary physical features entered are hair,ears, eyes, nose, philtrum, oral region, neck, hands/feet,chest, skin, abdominal, genitalia, and skeletal [7]. Diseases or conditions included in the My Family Health
Portrait tool [8] include cancer, clotting disorder, dementia/Alzheimer’s disease, diabetes, gastrointestinal disorder, heart disease, high cholesterol, hypertension,
kidney disease, lung disease, osteoporosis, psychologicaldisorder, septicemia, stroke/brain attack, sudden infant
death syndrome, and unknown disease (Fig. 1o). The
first four out of sixteen entry fields may also be used as

Tokutomi et al. BMC Medical Genetics (2017) 18:71

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Fig. 2 Fictitious pedigrees created by f-treeGC. a Fictitious ultimate pedigree, b A hypothetical pedigree representative of a family with vonHippel-Lindau syndrome shown in Fig. 1, partially modified from Bennett et al. [1, 7]. The clients are included in the 2nd generation (a) or in the
3rd generation (b) upon confirmation at system startup

Table 1 Correspondence table of f-treeGC

keys related to the multiple conditions of an affected individual (Fig. 1k, p). The “Show below symbol” box isfor showing the entry below each symbol, only if the box
on the left of the entry field is checked (Fig. 1q).

Client has a child

Client has NO children

Pedigree chart creation

Client (consultand) couple

Parents of clientChildren of client couple

Client (consultand)f-treeGC automatically creates a pedigree chart; thechart-creation process is visible for inspection on thescreen in real time (Fig. 1r). The “Show the PEDIGREE”
button (Fig. 1s) at the top of the screen displays a larger
chart (Fig. 2b). The user may additionally edit a pedigree
chart to visualize the larger chart with multiple displays.
A context menu appears when the family tree is rightclicked. The user may select “Add comment,” right-clickon the comment box, and then type the appropriate text.
Holding down the left mouse button allows the comment in the family tree to be moved and placed accordingly. The user may delete the comment, if required, byselecting “Delete comment”. By default, a pedigree chartdoes not include the name input (Fig. 1b, t) for privacy.

Husband’s (his) parents

Paternal grandparents

His siblings

Paternal uncles/aunts

His paternal uncles/aunts

Siblings of paternal grandfather

His maternal uncles/aunts

Siblings of paternal grandmotherHis divorced partners

Divorced partners of father

Wife’s (her) parents

Maternal grandparents

Her siblings

Maternal uncles/aunts

Her paternal uncles/aunts

Siblings of maternal grandfather

Her maternal uncles/aunts

Siblings of maternal grandmother

Her divorced partners

Divorced partners of motherTokutomi et al. BMC Medical Genetics (2017) 18:71

aPage 5 of 12

Front

ReversebcFig. 3 Foldable interview sheet named “f-sheet”. a Large sheet, b gathered interview sheets for each individual, and c accordion-folded sheet. In
diagram (a), the dashed-dotted lines, “-・-・-・-・-”, and broken lines, “- - - - -”, show the mountain fold and the valley fold, respectively

The user may see names by selecting “Show names” inthe context menu. To print or save an image of the pedigree, including names or other health conditions, the user
may capture a screen shot (Fig. 2b, Additional file 3), or
input the names manually in the “Remarks” box (Figs. 1uand 2a, Additional file 2).

Saving and reading the data

The genealogical information data may be saved as theoriginal format file (FTGC file) by clicking the “Save the
FTGC DATA” button (Fig. 1v), and shared between
computers that have f-treeGC installed. The created/
modified date and time may be changed as necessary before saving the data (Additional file 1c). In addition, theimage of the pedigree chart may be saved in PDF format
by clicking the “Save an IMAGE as PDF” button (Figs. 1t
and 2a). The file may be password-protected and/or
saved in a read-only format (Additional file 1c). A saved
file may be read by clicking the “Read the FTGC DATA”

button (Fig. 1w) at the top of the screen and selecting
the file.
Comparison of the pedigree symbols used

A comparison of the pedigree symbols used in f-treeGC
with those of several existing tools [8–11] is shown in
Table 2. f-treeGC complies fully with the international
recommendations of standardized human pedigree nomenclature [2], including common pedigree symbols,
pedigree lines, assisted reproductive technology symbols,
and pedigree symbols of genetic evaluation/testing information (Additional file 6).
System features and functions of f-treeGC as a family
history collection tool

A well-designed online family history tool from the US
Surgeon General, called My Family Health Portrait, isused for the collection and storage of family history data
[11, 12]. In addition, the MeTree software programTokutomi et al. BMC Medical Genetics (2017) 18:71

Page 6 of 12

Fig. 4 Overlay function of f-treeGC for consanguinity; a pedigree before (a) and after (d) overlay; the interview sheets of the wife (b, e) and a firstcousin (c, f)developed by the Duke Center for Applied Genomics
and Precision Medicine enables collection of family
health history and provides clinical decision-making support for more than 30 conditions such as cancer, cardiovascular diseases, liver, and diabetes [12, 13]. The Global
Alliance for Genomics and Health (GA4GH) provides
the GA4GH family history collection and clinical decision support tool inventory, and is open for submission.
The information collected by f-treeGC is shown in Table 3
and in Additional file 7 derived from the submission formof the GA4GH family history tools catalog [12].
Verification of the software and interview sheet

To verify that f-treeGC enables users without specialized knowledge of clinical genetics and graphical skills
to easily create medical pedigrees, we provided ninesubjects (six nurses and three clerks) with two scenarios (D, Duchenne muscular dystrophy; P, phenylketonuria) of fictitious family histories (Additional file 8),
and compared the pedigrees obtained by f-treeGC(Additional file 9) with those derived manually. The pedigrees were scored according to a system of allocation points(Additional file 8) based on the international standard [2]to examine the performance and usability of f-treeGC. The

creation time was indefinite, and we divided the trees into
two groups with different orders of scenarios applied. We
used Windows 7 as the OS for this test.
To verify that f-sheet improves the user experience fordata input to f-treeGC, we provided 47 high school students from one high school (males, N = 28; females,
N = 19; age range, 15–16 years; grade, the first year)with the software and data for two scenarios. Students
were randomly assigned to two groups: students of one
group created pedigrees for both scenarios (Additional
file 8) using f-treeGC without f-sheet (group TT; males,
N = 17; females, N = 6). Students of the other group firstcreated pedigrees for scenario D using f-treeGC without
f-sheet, and then created pedigrees for scenario P using
f-treeGC with a completed f-sheet (group TS; males,
N = 11; females, N = 13). The pedigrees with or without
f-sheet were scored using our points allocation system(Additional file 8) based on the international standard[2]; then, the scores were compared to examine theefficacy and usability of f-sheet. The creation time
was indefinite. The OS used for this purpose was
Windows 7.
The Wilcoxon signed-rank test and Mann-Whitney Utest were performed for statistical analyses, using

Tokutomi et al. BMC Medical Genetics (2017) 18:71

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Table 2 Comparison of the pedigree symbols used
Pedigree software packages

f-treeGC

PedigreeXP

Progeny Free Online
Pedigree Tool

Genial Pedigree
Draw

My Family Health
Portrait

Version1.01

2.1.0.169

Not described

2.0

3.4

Standard pedigree symbolsa
Name of proband/consultand

Yes

Yes

Yes

Yes

No

Family names

Yes

Yes

Yes

Yes

Yes

Historian

Yesb

No

Yesb

No

No

Date of intake/update

Yes

No

No

No

Yes

b

Reason for taking pedigree

b

Yes

No

Yes

No

No

Ancestry of both sides of the family

Yes

Yes

Yes

Yes

No

Age

Yes

Yes

Yes

Yes

No

Generation numbered with Roman
numerals I, II, III, etc.

Yes

Yes

Yesb

Yesb

No

Individual numbered 1, 2, 3, etc.

Yes

Yes

Yesb

Yesb

No

Individual

Yes

Yes

Yes

Yes

Yes

Affected individual

Yes

Yes

Yesd

Yes

Yes

Affected individual (> one condition)

Yesc

Yesc,d

Yes

Yes

No

Multiple individuals, number known

Yes

Yes

Yes

Yes

No

Multiple individuals, number unknown

Yes

Yes

Yes

Yes

No

Deceased individual

Yes

Yes

Yes

Yes

Yes

Consultand

Yes

No

No

Yes

No

Proband

Yes

Yesd

Yesd

Yes

No

Stillbirth (SB)

b

Yes

No

No

No

No

Pregnancy (P)

Yes

Yes

Yes

Yes

No

d

Spontaneous abortion (SAB)

Yes

Yes

Yes

Yes

No

Affected SAB

Yes

Yes

Yesd

No

No

Termination of pregnancy (TOP)

Yes

Yes

No

Yes

No

Affected TOP

Yes

Yes

No

No

No

Ectopic pregnancy

Yesb

Yesb

No

Yes

No

Relationship line

Yes

Yes

Yes

Yes

Yes

A break in relationship line

Yes

Yes

Yes

Yes

No

Divorced partner

Yese

Yes

Yes

Yes

No

Consanguinity

Yes

Yes

Yes

Yes

No

Multiple gestation, monozygotic

Yes

Yes

Yes

Yes

No

Multiple gestation, dizygotic

Yes

Yes

Yes

Yes

No

Multiple gestation, unknown

Yesb

No

Yesb

No

No

Multiple gestation, trizygotic

Yes

Yes

Yes

Yes

No

Family history not available/known
for individual

Yes

No

No

No

No

No children by choice or reason
unknown

Yes

No

Yes

Yesd

No

Infertility

Yes

No

Yes

Yesd

No

Adoption

Yes

Yes

Yes

Yes

Yesd

Ovum or sperm donor

Yes

No

No

Yes

No

Surrogate (gestational carrier)

Yes

No

No

Yes

No

Tokutomi et al. BMC Medical Genetics (2017) 18:71

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Table 2 Comparison of the pedigree symbols used (Continued)
Yesb

Yesb

Yes

Yesb

No

Carrier

Yes

d

Yes

f

Yes

Yes

No

Asymptomatic/presymptomatic carrier

Yes

No

No

Yes

No

Evaluation

Uninformative study

b

Yes

b

Yes

b

Yes

b

Yes

No

Affected individual with positive evaluation

Yesb

Yesb

Yes

Yesb

No

a

Bennett et al., 2008 [2]By using “Remarks”, “Comment”, “Notes”, or “Annotated Text”
Up to four conditionsdDifferent symbols used from the recommended common pedigree symbolseLimited to three individuals (consultand couple with children, or parents of consultand without children)f
By using “Apply symbols”
bc

Statcel4 software (OMS Ltd. Publishing, Saitama, Japan).
Significance was set at p < 0.05.
The family trees obtained using f-treeGC had higherscores than those that were manually created (p < 0.001)(Table 4). Moreover, the input time and family tree
scores of trees created using f-treeGC were not affectedby the difference in scenario content, order of application, or the qualifications of each user (Table 4). Furthermore, the scores of the family trees created using ftreeGC with a completed f-sheet were higher than thosecreated using f-treeGC without f-sheet (p < 0.01) (Table 5).

Discussion
In the present study, we report the development of ftreeGC, a free stand-alone application built as a crossplatform runtime system. f-treeGC is capable of automatically creating a medical family tree compliant withinternational standards [2] by filling out available family

tree information on a medical interview sheet (Fig. 1).
Family histories are entered as both structured data andfree text by the clinician or data entry clerk, and collected from patients or through f-sheet, which is a
printed paper version of the questionnaire in f-treeGC(Fig. 3, Additional file 4). The family history data are
stored in a computer in the original format file. f-treeGC
may be used for collecting family health histories and creating pedigrees for individuals participating in situations
such as primary care, genetic counseling, or genome cohort studies. The targeted clinical populations are recipients of primary and specialty health care facilities.
f-treeGC simplifies the process of creating pedigrees
by confirming whether the client has offspring at systemstartup (Table 1, Additional file 1a) and by using theoverlay function for confirming consanguinity (Fig. 4).
Here, we show that f-treeGC, which is fully compliant
with international recommendations for standardized

Table 3 f-treeGC information
ProvenanceAcademically developed

Tool URL

http://www.iwate-med.ac.jp/hospital/clinics/medical/m26/

Target clinical population

Primary care and specialty

Family history information - source

Multiple sources

Family history information - data format

Both structured and free text

Family history information - analysis

ManualResult recipients

ClinicianData storage

Store in the original format file

Discrete data integration readiness

Application programing interfaces (API)Consent documentation

Implied consent only

System features - platforms

Windows and Macintosh
Built in Adobe Air

System features - architectureStand-alone

System features - security

Password security protection
Read-only modeStandard pedigree symbols
Other functions

Fully compliant
CustodyPregnancy with twins or multiples

Tokutomi et al. BMC Medical Genetics (2017) 18:71

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Table 4 Comparison of pedigree scores and creation time for each factor
Factors

Median (Range)

Method (manual method vs. f-treeGC software)

ManualP valueNf-treeGC

Score (%) of both scenarios

59.5(23.7)

86.4(25.8)

0.00019***

18

Score (%) of scenario D

58.8(14.7)

86.8(16.2)

0.00769**

9

Score (%) of scenario P

60.2(23.7)

86.0(25.8)

0.00742**9

Order of scenarios (D to P vs. P to D)

D to P

P to D

55.9(11.8)

61.0(14.7)

0.32312

Time (sec/individuals) of scenario D by
the manual method

42.5(18.8)

25.9(12.5)

0.01390

Score (%) of scenario P by the manual
method60.2(11.8)

57.5(23.7)

1.00000

5×4

Time (sec/individuals) of scenario P by the
manual method

26.7(16.3)

28.8(33.3)

0.32516

5×4

Score (%) of scenario D by f-treeGC

83.8(16.2)

87.5(13.2)

0.61980

5×4Time (sec/individuals) of scenario D by
f-treeGC

65.0(49.4)

61.9(23.4)

0.46243

5×4

5×4
*

5×4

Score (%) of scenario P by f-treeGC

86.0(25.8)

87.6

(8.5)

1.00000

5×4

Time (sec/individuals) of scenario P byf-treeGC

46.7(25.4)

51.5(44.3)

0.32719

5×4

9

1st

2nd

Score (%) by the manual method

55.9(23.7)

60.3(14.7)

0.44127

Time (sec/individuals) by the manual
method40.0(37.5)

26.7(19.2)

0.01086

Score (%) by f-treeGC

83.9(18.9)

86.8(25.8)

0.67840

9Time (sec/individuals) by f-treeGC

59.2(65.6)

50.4(38.5)

0.13864

9

Qualification (nurse vs. clerk)

Nurse

Wilcoxon signed-ranksum test

Mann-Whitney U-test

Score (%) of scenario D by the manual
methodOrder of scenarios (1st vs. 2nd)

Statistics*

Wilcoxon signed-ranksum test

9

Clerk

Mann-Whitney U-test

Score (%) by the manual method

61.0(23.7)

54.1(17.2)

0.13339

12 × 6Time (sec/individuals) by the manual
method30.8(40.8)

26.3(45.4)

0.67310

12 × 6

Score (%) by f-treeGC

86.4(17.2)

86.8(25.8)

0.8510312 × 6Time (sec/individuals) by f-treeGC

57.1(53.1)

39.4(47.9)

0.18955

12 × 6*p < 0.05**p < 0.01***p < 0.001

Table 5 Comparison of pedigree scores using f-treeGC with or without f-sheet
Factors

Median (Range)

Group (TT vs. TS)TT

P valueN

TS

Mann-Whitney U-test

Score (%) of scenario D

89.7(10.3)

87.5(26.5)

0.0196*23 × 24

Score (%) of scenario P

88.8(24.5)

92.3(17.3)

0.0109*23 × 24

Scenario (D vs. P)

DP

Wilcoxon signed-ranksum test

Score (%) of group TT

89.7(10.3)

88.8(24.5)

0.6922

Score (%) of group TS

87.5(26.5)

92.3(17.3)

0.0018*p < 0.05**p < 0.01

Statistics

23
**

24

Tokutomi et al. BMC Medical Genetics (2017) 18:71

human pedigree nomenclature (Table 2), is highly usefulfor creating pedigree charts for applications in genetic
counseling.
However, the present study is not without limitations.
As f-treeGC is only capable of creating a pedigree up to
three generations, this software is currently unsuitablefor creating large pedigrees. There are no auxiliary input
functions for medical terms, pedigree-overlay function,
nor a calculator for determining disease risk. f-treeGC is
not adapted for compliance with Health-Level 7 (HL7)
standards. Although numerous health and medical conditions exist [13], f-treeGC is limited to only sixteen
medical conditions per person.
Low quality of family history data collected presents achallenge in pedigree analysis [14]. Before collecting
family health histories, users should guide patients regarding what to inquire of relatives, as the amount andaccuracy of the family history is limited. The Iwate Tohoku Medical Megabank Organization conducts genetics
workshops mentored by medical geneticists or genetic
counselors to highlight the importance of family healthhistory before recruiting participants for cohort studiesof the TMM project.
Family history, the ultimate genetic tool [15], is the mostcost-effective and well known “genetic test” in clinicalpractice today [16]. However, recording family trees according to standard recommendations generally requires
knowledge of graphical interfaces and clinical genetics [7].
In 2016, the National Human Genome Research Institute(NHGRI) convened a Family Health History Tool Meetingat the National Institute of Health (NIH) for identifying
and sharing successful approaches to using family healthhistory tools, and for identifying unresolved issues and potential solutions that may be addressed by policy, research,
and/or collaborative efforts. The removal of barriers tohealth equality in populations with low levels of literacy,and exploration/expansion additional technological approaches for family health history collection was discussed
in this meeting [14].
Six years have passed since the Great East Japan
Earthquake and Tsunami. However, health and medical services has not been fully restored to date. The
TMM project initiated two prospective cohort studies
in the Miyagi and Iwate prefectures, which include
the disaster-stricken areas: a population-based adultcohort study, in which 80,000 participants were recruited, and a birth and three-generation cohort
study, in which 70,000 participants, included fetuses
and their parents, siblings, grandparents, and extended family members, were recruited [4]. Collectionof significant numbers of family health histories by
conventional pedigree-drawing software programs ischallenging in these regions owing to the lack of goodinternet service and personal computers. We used f-

Page 10 of 12

treeGC for genetic counseling at our institution, collecting approximately 100 patient histories and corresponding data, which would have taken a genetic
counselor around twenty minutes in a clinical setting.
In contrast, the software took about one minute perperson to input two clinical scenarios at the verification experiment (Table 4). Since the use of f-treeGC
in combination with f-sheet simplifies the process ofcollection of many numerous health histories andpedigrees (Table 5), its application is not limited toheredity clinics, but also to large-scale genome-cohort
studies that handle large amounts of genetic information obtained through interviews at a single recruiting
event.
The main advantages of f-treeGC are collection ofseveral family histories for large-scale cohort studies
in a short period of time, easing the burden of collection of genealogical information and creation of pedigree
charts in remote medical practice by less experienced
medical practitioners. In addition, the present tool facilitates online genetic counseling owing to its complete
compliance with the international recommendations forstandardized human pedigree nomenclature (Table 2).
Public awareness regarding the basic principles of genetics should be considered for the improvement of public health. Familial/pedigree information is valuable forvariant filtering in high-throughput sequencing studies[17, 18]. Molecular approaches for the identification of
disease-associated genes generally begin with pedigreebased methods, including positional cloning and foundergene approaches, prior to the use of pedigree-independent
methods such as candidate gene approaches and genomewide association studies [19]. With the recent explosion inwhole-genome sequencing, linkage analysis has emerged
as an important and powerful analytical method for theidentification of genes involved in disease etiology, often
in conjunction with whole-genome sequencing filtering
approaches [20]. From this perspective, f-treeGC is a useful tool, not only for facile and accurate pedigree analysis,
but also for conveniently collecting numerous family histories and pedigrees simultaneously. In future, we aim to
add a calculator function for determining disease risk, an
auxiliary input function for medical terms, a search function for family health conditions from free text, an adaption for HL7, and a pedigree-overlay function to thepresent f-treeGC software.

Conclusions
The f-treeGC software enables collection of family
health history and automatically creates a medical family
tree simply by filling out family tree information on a
medical interview sheet, or by inputting the informationin the questionnaire directly from the f-sheet.

Tokutomi et al. BMC Medical Genetics (2017) 18:71

Availability and requirements
Project name: TMM project
Project home page: http://www.amed.go.jp/en/program/list/04/01/042.html
Operating systems: Windows and Macintosh
Programing language: ActionScript 3.0
Licence: f-treeGC is a non-copylefted software, and iscopyrighted by the Iwate Medical University and Holonic Systems, Ltd. The source code is not available.
Additional files
Additional file 1: Dialog boxes of f-treeGC (a) Confirmation of whether
or not the client has a child at system startup, (b) Configuration of thecolor for affected individuals, (c) File attribute setting for changing thecreated/modified date and time, setting a password, and converting toread-only. (PPTX 141 kb)
Additional file 2: A pedigree file of Fig. 2a; fictitious ultimate pedigree,
partially modified from Bennett et al. [1, 7]. (FTGC 20 kb)
Additional file 3: A pedigree file of Fig. 2b; a hypothetical pedigree
representative of a family with von Hippel-Lindau syndrome, partiallymodified from Bennett et al. [1, 7]. (FTGC 9 kb)
Additional file 4: f-sheet; a printed paper version of the questionnairein f-treeGC. (XLSX 57 kb)
Additional file 5: A pedigree file of Fig. 4d; with respect toconsanguinity, f-treeGC shows only marriages between first cousins using
the overlay function. (FTGC 8 kb)
Additional file 6: List of symbols used in f-treeGC; f-treeGC fullycomplies with the international recommendations of standardized humanpedigree nomenclature [2]. (PDF 8 kb)
Additional file 7: Current family history collection tools and f-treeGC;
partially modified from GA4GH family history collection and clinicaldecision support tool inventory 6–9-16 v4.1 by Clinical Working Group of
the Global Alliance for Genomics and Health. (XLSX 18 kb)

Page 11 of 12

Availability of data and materials
The datasets supporting the conclusions are included in this article and in
the additional files. The f-treeGC software program is available at no monetarycharge at the Iwate Medical University Hospital website, http://www.iwatemed.ac.jp/hospital/clinics/medical/m26/, and the f-sheets are available at nomonetary charge as additional files with this article.
f-treeGC is a non-copylefted software, and is copyrighted by the Iwate
Medical University and Holonic Systems, Ltd. The source code is not available.
f-treeGC is written in ActionScript 3.0, and may be run on Adobe AIR, which is across-platform runtime system. f-treeGC is supported by both Windows(Windows 7, 8, and 10) and Macintosh (OS X). An application for the f-treeGC
software program is under review for the international Patent Cooperation
Treaty (PCT/JP2016/078494).
f-sheet is copyrighted by the Iwate Medical University and registered as autility model in Japan (3204531).
Authors’ contributions
TT was responsible for the execution of the research project and for writing
the first draft of the manuscript. AF designed, organized, and reviewed theresearch project and reviewed and critiqued the manuscript. KY wasresponsible for manual preparation, checking of software operation, andcomparison of pedigree software packages. YB was responsible for computer
programming. TH reviewed the manuscript. AS was responsible for manual
preparation and reviewed the manuscript. All authors read and approved thefinal manuscript.
Ethics approval and consent to participate
Ethical approval for our study was obtained from the institutional review
board of the Health Science University of Hokkaido (Approval ID: 174). This
study was conducted in accordance with the Declaration of Helsinki,Japanese Act on the Protection of Personal Information, and Japan Ethical
Guidelines for Medical and Health Research Involving Human Subjects. We
obtained informed consent from parents of all the students enrolled in ourstudy.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.

Additional file 8: Two scenarios for the creation of pedigrees; scenario
D (Duchenne muscular dystrophy) and scenario P (phenylketonuria). Any
resemblance to real persons and pedigrees, living or dead, is purely
coincidental. (XLSX 12 kb)

Publisher’s Note

Additional file 9: Model pedigrees of scenarios outlined (a) Scenario D,(b) scenario P. (PPTX 389 kb)

Author details
1
Department of Clinical Genetics, School of Medicine, Iwate Medical
University, Morioka, Iwate 020-8505, Japan. 2Division of Innovation and
Education, Iwate Tohoku Medical Megabank Organization, Iwate Medical
University, Shiwa, Iwate 028-3694, Japan. 3Holonic Systems Ltd., Shiwa, Iwate
028-3441, Japan. 4Division of Biomedical Information Analysis, Iwate Tohoku
Medical Megabank Organization, Iwate Medical University, Shiwa, Iwate
028-3694, Japan.

Abbreviations
GA4GH: Global Alliance for Genomics and Health; TMM project: Tohoku
Medical Megabank project

Acknowledgements
The authors thank the members of the Iwate Tohoku Medical Megabank
Organization for suggestions and comments; Dr. Hiromasa Ono and
Dr. Hidemasa Bono, Database Center for Life Science, for manual preparation;
the members of Akita IP Firm for valuable suggestions; the members of
Editage for English proofreading and valuable comments; Dr. Tohru Ohta,
Dr. Rie Takai, and Dr. Norio Niikawa, Health Science University of Hokkaido,
for experimental support and valuable comments; and Ms. Fumiyo Nakayama,
Iwate Tohoku Medical Megabank Organization, for her assistance in preparing
the manuscript; Mr. Yusuke Sakurai, Iwate Medical University Hospital, forgeneration of the website.

Funding
This research is supported by the Ministry of Education, Culture, Sports,
Science and Technology (MEXT), Japan Agency for Medical Research andDevelopment (AMED), and Iwate Industry Promotion Center.

Springer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.

Received: 20 December 2016 Accepted: 27 June 2017

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