Fundamental knowledge taught in compulsory education for effective genetic counseling: a qualitative study of descriptions in textbooks

In genetic counseling, information must be provided in ways that the client and general public can understand to ensure that decisions are made autonomously. To realize this, we must assess the extent of knowledge held by the general public regarding genetics. To identify the client’s original knowledge before genetic counseling, we explored the fundamental knowledge related to genetic counseling that is taught in Japanese compulsory education. A qualitative study was conducted. We selected 50 textbooks for compulsory education (Japanese, social studies, science, health and physical education, technology and home economics, morality, and life) that had been used in more than half of the districts in Japan. The text data were analyzed using qualitative content analysis, and quantitative data were analyzed for methodological triangulation. Codes, subcategories, and categories were generated from the contexts that met the following criteria: the contents included in the official textbook for clinical geneticists, contents derived from such descriptions that were related to genetic counseling, and contents clearly related to genetics. Among the 50 textbooks, 33 textbooks contained fundamental knowledge regarding genetic counseling. A qualitative content analysis identified four major categories: (1) basics of genetics, (2) understanding and control of diseases, (3) efforts and barriers to the realization of a harmonious society, and (4) technology and humans. We found that fundamental knowledge related to genetic counseling is directly or indirectly taught in compulsory education. Our results are an important resource for understanding the client’s knowledge baseline and will be helpful for effective genetic counseling.


Introduction
Genetic counseling is the process of helping people understand and adapt to the medical, psychological, and familial implications of genetic contributions to disease (National Society of Genetic Counselors ' Definition Task Force et al. 2006). With the completion of the Human Genome Project in 2003 and the development of next-generation sequencers since 2005, comprehensive genomic analysis has become possible, and variations in each person's genetic information have been revealed. Although genetic medicine was previously focused on specific congenital diseases, genetic information has become indispensable in various medical fields. Hence, genetic counseling is becoming necessary, and clinical genetics professionals, such as clinical geneticists and certified genetic counselors, are facing supporting clients with various backgrounds.
Misunderstandings concerning genetics may affect coping and testing, treatment, and reproductive decisions (Klitzman 2010). To help clients make informed decisions, which are essential for their health, clinical genetics professionals provide the necessary information to clients. However, clients may misunderstand the genetic information even after genetic counseling (Browner et al. 2003;Gurmankin et al. 2005). To achieve effective provision of information, it is crucial to consider the client's level of understanding by selecting appropriate terms and organizing the information. Greater learning effects would be expected by communicating the information based on the knowledge of the recipients. For example, the admission policy of university sets the level of knowledge of students at the time of admission (Ministry of Education, Culture, Sports, Science and Technology; MEXT 2022a). The curriculum policy and the diploma policy are designed based on this. Thus, the education based on the knowledge of recipients is realized. Similarly, in genetic counseling, information may be effectively provided by understanding the recipient's initial knowledge. Every citizen could be a client of genetic counseling. Therefore, it would be helpful to determine the common fundamental knowledge of the public to effectively provide the necessary information.
In this study, we focused on compulsory education. Among various information sources from which clients obtain knowledge about genetics, compulsory education is the only way that knowledge is commonly transmitted to the public. Compulsory education is intended to build a foundation to enable each child to live a happy life, and it forms the foundation for all education (MEXT 2022b). In Japan, all children are required to study in elementary school and lower secondary school for 9 years (compulsory education) (MEXT 2022c). Moreover, compulsory education is standardized using textbooks certified by the Ministry of Education, Culture, Sports, Science, and Technology-Japan (MEXT 2022d). This implies that the content of the textbooks used in compulsory education can be regarded as the knowledge that is commonly transmitted to the public.
In genetic counseling, clients need not only genetic information but also a wide range of practical knowledge about the disease, including natural history, treatment, health care, prevention, and social resources (Japanese Board of Medical Genetics and Genomics, Clinical Genetics 2021). Such varied knowledge may be described in various textbooks used in compulsory education. Although some textbook surveys have been conducted to improve genetic education in the compulsory education system, no study has attempted to understand the fundamental knowledge related to genetic counseling as described above. Therefore, this study aimed to explore the knowledge taught in compulsory education using both qualitative and quantitative approaches to reveal the client's fundamental knowledge. We believe that this research will be useful for understanding the client's knowledge baseline and will be helpful for effective genetic counseling.

Qualitative approach and research paradigm
We selected a qualitative methodology because it is useful for exploring areas that have not been extensively researched (Denzin et al. 1994). The Standards for Reporting Qualitative Research (SRQR) checklists were used in this study (O'Brien et al. 2014).

Researchers' backgrounds and reflexivity
The research team consisted of three graduate students (ES, HO, and KM) enrolled in the genetic counseling course and studying genetic counseling and clinical genetics, two clinical geneticists (TY and SK) who were faculty members in the Department of Medical Ethics and Medical Genetics, and two qualitative research experts in medical communication (TF and MI). The study was conceptualized by ES and TY, and the study design was planned by ES, TY, TF, and MI. The data were collected by ES, TY, HO, and KM. Qualitative analysis was then conducted by ES, TY, TF, MI, HO, and KM. Under the supervision of TF and MI, the analysis was performed by ES and TY with the assistance of HO and KM. The paper was written by ES and TY, supervised by MI and SK.

Sampling strategy
Textbooks for compulsory education are selected for each of the 583 districts in Japan. To target the textbooks that would be most commonly used as of 2021, we counted which textbooks were selected for each subject in each district. Subsequently, we selected 50 textbooks covering seven subjects (Japanese, social studies, science, health and physical education, technology and home economics, morality, and life) that had been selected in more than 50% of the districts. In lower secondary school, social studies are divided into geography, history, and civics. The selected subjects were expected to contain statements related to genetic counseling (excluding mathematics, English, art, drawing, and music).

Data collection methods
The main text descriptions of the 50 textbooks were digitized using optical character recognition software (Yomitori Kakumei, Source Next, Japan), and typographical errors were corrected by reading directly or using the proofreading function. Moreover, the entire text was carefully read by ES, and the information and keywords contained in the text were listed (see the "Data analysis" section for explanation of keywords). The text data were managed using Microsoft Excel (Microsoft, Seattle, USA) and classified into text, table of contents, grade, subject, and publisher (Table 1).

Data analysis
Data analysis was performed using the Mayring's qualitative content analysis approach (Mayring 2000). First, the first researcher read the entire text multiple times to gain familiarity with the data and made notes of initial findings and impressions. During this process, keywords were highlighted to improve the subsequent analysis (the selection of keywords is described below). Second, code labels emerged that met the following criteria: the contents included in the official textbook for clinical geneticists (Japanese Board of Medical Genetics and Genomics 2021), the contents derived from such descriptions that were related to genetic counseling, and the contents related to genetics (description related to diseases, disorders, diversity, and etc.). The codes often came directly from the text and produced the initial coding scheme. Codes that were conceptually similar were placed in a new code. Subsequently, authors TY, TF, and MI reviewed the produced codes. Third, codes that were semantically related were organized into subcategories. Moreover, related subcategories were organized into categories. Afterward, ES and authors TY, HO, and KM discussed any discrepancies among codes, subcategories, and categories until a consensus was reached. The data Table 1 Textbooks containing fundamental knowledge related to genetic counseling and its descriptive proportion Among the 50 analyzed textbooks, 33 textbooks contained fundamental knowledge related to genetic counseling. Table 1 shows the descriptive proportion by grade level. In lower secondary school, social studies is divided into geography, history, and civics. In cases where the data were extracted from multiple publishers, the average values of the data are listed. The sources are represented by subjects and grades; alphabet abbreviation indicates the subject, and numbers indicate the grade. However, there are some cases where the grade was not specified (e.g., J2 indicates a Japanese textbook for the second grade of elementary school). Grades were indicated as follows: E: elementary school, LS: lower secondary school (e.g., E2 indicates the second grade of elementary school). The number of textbooks indicates "the total number of textbooks that contained the object description/the total number of textbooks surveyed" were formulated inductively into categories in a step-bystep manner.
Owing to the large volume of the entire textbook, we used keywords to maintain analytical quality. The keywords defined here were as follows: (1) 704 keywords set in the behavioral goals of clinical geneticists (Japanese Board of Medical Genetics and Genomics, Clinical Genetics 2019) and (2) paraphrases and related phrases of (1). For example, keywords (1) such as DNA, gene, respect for diversity, and fetus generate keywords (2) including chromosomes, diversity, and baby (Supplementary Table 1). To select keyword (2), we used two methods: a close reading of the entire text and KH coder 3 (Higuchi 2016). KH coder is a free software for quantitative text analysis, and it has a morphological analysis function to extract words from text data. This allows us to obtain a list of words that appear in the textbook. With this, we confirmed all the words in the textbook and selected keywords (2) as defined above. With these keywords highlighted, we conducted the analysis by reviewing the entire text, including those that did not contain the keywords. Finally, for methodological triangulation, we calculated the proportion of descriptions in each textbook and the amount of descriptions by category, in addition to qualitative content analysis.

Results
The survey indicated that 33 of the 50 textbooks included foundational knowledge related to genetic counseling (Table 1). Evidently, the proportion of descriptions was higher in science, health, technology, social studies, Japanese, and morality, in that order. The textbooks of Japanese and morality included descriptions related to genetic counseling in many grades. Four categories and 15 subcategories were generated using qualitative content analysis ( Table 2). The results are described below. For reference, all the codes summarized in the four categories are listed (Supplementary Table 2).

Category 1. Basics of genetics
The textbook explained the most basic aspects of genetics: sexual reproduction, mitosis and meiosis (somatic cell and germ cell division), and Mendelian inheritance. Science textbooks include a chapter on biology at each grade. Students first learn that life begins at fertilization in the fifth grade of elementary school. They then learn more about cell division and Mendelian inheritance in the third grade of lower secondary school to deepen their understanding of the topic. Specifically, the textbook explained the difference between mitosis and meiosis along with the division of chromosomes, and then explained Mendelian laws of dominance and segregation.
"The characteristics of offspring reproduced by sexual reproduction, such as killifish, may be the same or different from those of their parents. Thus, unlike organisms reproduced by asexual reproduction, in organisms reproduced by sexual reproduction not all the characteristics of the offspring will be the same as those of the parents. (SC9)" "Cell division during germ cell production differs from mitosis in that chromosome number is halved. This division is called meiosis. Fertilization of an egg and a sperm with half the number of chromosomes results in the child having the same number of chromosomes as the parent. Thus, by meiosis and fertilization, the chromosomes of the Mitosis and meiosis (somatic cell and germ cell division) 18 Mendelian inheritance 21 Biological evolution and diversity 4 Individual differences at the DNA level 6 Disease causation Understanding and control of diseases 11 Cancer development, causation, and risk factors 6 Juvenile and congenital diseases 6 Harmonious coexistence with diverse people Efforts and barriers to the realization of a harmonious society 23 Understanding diversity and respect for individuals 11 Social welfare 2 Promotion of a barrier-free society 4 Prejudice and discrimination due to innate characteristics 5 Scientific technology and human evolution Technology and humans 19 Benefits and concerns of gene technology parent and the offspring are kept at the same number.… When pure lines with allelomorphic traits are crossed, the trait that appears in the offspring as a round seed is called a dominant trait, and the trait that does not appear in the offspring as a wrinkled seed is called a recessive trait. … Suppose that the combination of genes carried by a pure line that produces round seeds is denoted by AA. Similarly, suppose that aa is the combination of genes carried by a pure line that produces a wrinkled seed. The paired parental genes are separated by meiosis, placed in separate germ cells, and then paired again by fertilization. All gene combinations in the child (fertilized egg) will be Aa. ...Paired genes enter separate germ cells by meiosis. This is called the law of segregation. (SC9)" Moreover, it was described that novel changes in DNA sequence can occur during chromosome replication, which may produce traits that do not appear in the parents (de novo mutation).
"Genes in chromosomes are not unchangeable. When chromosomes are replicated, changes may occur in DNA, the main body of the genes, and these changes may be inherited to the offspring. In such cases, traits that did not appear in the parents or ancestors may appear in the offspring.(SC9)" Although these reproductive mechanisms are primarily described in the textbook of science, the textbook of health included a description of pregnancy, which also explained reproduction from a different perspective.
"At puberty, the pituitary gland in the brain secretes gonadotropic hormone, which causes the growth and development of reproductive organs (ovaries in girls and testes in boys). …Sperm produced in the testes of the male are ejaculated in vagina of the female and combine with the ovulated egg in the fallopian tube to form a fertilized egg.(H7)" Various genetics-based phenomena were also described in the textbook. For example, in the textbook of science, the chapter following Mendelian inheritance dealt with the evolution of organisms. It explained the biological evolution and diversity resulting from the accumulation of genetic changes.
"Evolution is also closely related to changes of genes. A slight change of a gene that determines a trait may be inherited to offspring. As these genes are passed from generation to generation over time, the characteristics of the offspring change. (SC9)" Evolution of organisms was also described in Japanese. In addition, other examples regarding individual differences at the DNA level were raised.
"Drugs have a therapeutic effect and side effects, which are undesirable effects. The manifestation of side effects depends on the constitution and condition of the user and its way of use. (H7)" "Bone marrow transplantation is a procedure of bone marrow replacement with another person's bone marrow, which is responsible for blood production, so that healthy blood can be produced. There are so many different types of white blood cells. Only one in four siblings has the same type of it, and in other cases, even blood relatives rarely have the same type. (M7)" Accordingly, it was revealed that textbooks contained basic knowledge of genetics and genetic phenomena linked to daily life. Among the knowledge related to genetic counseling identified in this study, descriptions classified in category 1 were the most numerous, accounting for 43.4% of the total (Table 3). In particular, the volumes of description in science and Japanese were higher than in other subjects.

Category 2. Understanding and control of diseases
In lower secondary school textbooks of health and physical education, there are chapters regarding the component factors of health and disease in the section on healthy life and disease prevention, where disease causation is explained. Specifically, it classified age, sex, immunity, and heredity (constitution) as the individual factors, and lifestyle Table 3 Categories generated by analysis and the volume of descriptions categorized in each category The description related to genetic counseling was counted in each category shown in Table 2 Subject The chapter "Prevention of lifestyle diseases" included an explanation on cancer development, causation, and risk factors. Specifically, it was described that cancer was caused by the accumulation of somatic mutations, which are affected by lifestyle habits and viral infections, suggesting that we should develop an appropriate lifestyle and aim for early detection and treatment through medical checkups.
"Cancer is a disease in which the genes in normal cells are damaged and transformed into cancer cells, which grow in an uncontrolled manner and disrupt the function of organs. (H7)" "Cancer can be caused by a variety of factors, including lifestyle habits such as smoking, excessive alcohol consumption, inappropriate diet, lack of exercise, and bacterial and viral infections. Effective cancer prevention that can be done by yourself is establishment of appropriate lifestyle. Early detection of abnormalities through health checkups and cancer screening is important for cancer treatment and recovery. (H7)" As mentioned above, the topic of illness and health is typically covered in the textbooks of health and physical education; however, it has also been included in morality textbooks. For example, the characters in the stories often had juvenile and congenital diseases, such as visual impairment or congenital neuroblastoma.
"When he was born, his left eye vision was blind and his right eye vision was 0.1. But he grew up to be a good swimmer. By the time he reached the upper grades, he gradually lost vision in his right eye. He felt that his eyesight was getting worse. (J8)" "At the age of five, he was diagnosed with neuroblastoma and died at the age of eleven. (M5)" Although there is no direct mention of heredity, one story of a mother and a son suffering from the same heart disease was described.
"The mother had a serious heart disease. … At seven months of age, Tomo-kun was found to have the same heart disease as his mother. The father's eyes suddenly went completely dark. (M4)" In this way, compulsory education provides information about the disease and about the actual living conditions of patients with the disease. The descriptions classified in category 2 accounted for 8.2% of the total. In particular, the amount of descriptions in health and physical education and morality was relatively high (Table 3).

Category 3. Efforts and barriers to the realization of a harmonious society
The textbooks explained a harmonious society as one in which diverse people can participate and contribute to society and then mentioned the concept of society and specific efforts to realize such a society. In particular, the fact that we should understand diversity and respect for individuals were taught in various grades and subjects. For example, textbooks of Japanese and morality used this information as a theme for stories several times. The textbooks of social studies explained that any kind of discrimination was forbidden by law.
"There will be people of various generations, people with and without disabilities, people of various nationalities, people of different cultures and languages, and people from all walks of life. Living together with such surrounding people is called Harmonious coexistence. (HE)" "Even if a newborn baby, everyone has his or her own personality and is a full-fledged human being, no matter how tiny he or she may be. (M8)" "No human being should be discriminated against because of his or her race, gender, or status at birth, or be arrested for having a different opinion. …In particular, discrimination based on 'birth' is in violation of the fundamental principle of the Constitution of Japan, which is respect for fundamental human rights, and must never be tolerated. (S)" More specific initiatives included social welfare and promotion of a barrier-free society. In social studies, the chapter "Our Life and Politics" in a textbook for 6th grade in elementary school introduced a certain social welfare facility, and the textbook for lower secondary school (civics) explained the social welfare system in the chapter "Our Life and Economy." In the textbooks of morality, such welfare facilities appeared in some stories.
"Even in recent years, women, the elderly, and people with disabilities are often disadvantaged in hiring and promotion, and have difficulty finding work. … Social welfare supports those who are vulnerable in society, such as the elderly, people with disabilities, and children. (Sc)" "Mei-san and her classmates researched and presented about welfare programs for the elderly and people with disabilities. 'Kijibato' is a facility where people with disabilities are trained to work and find jobs in order to support their independent lives. (S6)" "This facility is a welfare facility designed to provide a place to work for people who are unable to work due to disabilities and to assist them in becoming self-supporting. (M9)" The need for a barrier-free environment was also discussed in various textbooks, including Japanese, social studies, and health and physical education.
"From the viewpoint of city design, a barrier-free transportation environment is now being developed so that all people, including infants, the elderly, and people with disabilities, can pass through safely. (H7)" While respect for diversity has spread throughout society, there are also instances of prejudice and discrimination due to innate characteristics. Textbooks of social studies and morality picked up on this as follows: "All human beings are equal and have the right to equality. However, discrimination based on prejudice still remains. (Sc)" "Germany thoroughly discriminated against Jews and sent them to concentration camps around the country, including Auschwitz, where they were forced to work and murdered.

(Sh)" "Born to internationally married parents, I had a face that was slightly different from the children around me. I was often teased about it since my early elementary school days. I would try to laugh it off or say, 'Stop it!' But the teasing never stopped, and every day I wished I could get out of it. (M8)"
As mentioned above, the textbooks covered positive content toward a harmonious society as well as case studies related to events that could be barriers to such a society. Category 3 descriptions accounted for 37.0% of the total, indicating that they were often included in social studies, morality, and Japanese (Table 3).

Category 4. Technology and humans
The Japanese textbook for 6th grade in elementary school included the theme of science technology and human evolution and stated that we need to consider not only a technological aspect but also an ethical aspect in our use of science and technology.
"I believe that a future-thinking way of life is now required. What will happen if we live in such a way? …If we use our imagination in this way, we can come up with a society in which everyone can live comfortably. (J6)" In addition, as a scientific technology, several textbooks gave examples of gene technology applied in various fields, explaining the benefits and concerns of gene technology. The textbook of technology in lower secondary school explained that while genetic engineering technology contributes to food production, its impact on nature is a matter of concern.
"Technology and wisdom for growing organisms produces not only safe and abundant foodstuffs, but also pharmaceuticals and other products useful for human health, as well as fuels such as bioethanol. On the other hand, there is concern about the effect to the human body and human life and the natural world of the technology to manipulate genes to improve their traits more suitable for specific purposes and the herbicides and insecticides used in the process of growing plants.

(T3)"
The textbook of morality also stated that the development of iPS cells would contribute to disease treatment. The textbook of social studies (civics) stated that although gene technology is expected to be useful in treating intractable diseases, there is concern that it may result in genetic discrimination.

"Recent developments in science and technology have resulted in some difficult issues about life and human rights. For example, gene technology is expected to be useful in the treatment of intractable diseases, but since it is related to the core of life, there is an ongoing debate about whether it should be left up only to academic freedom. …In addition, there is concern that genetic diagnosis, which can measure the possibility of contracting diseases caused by genes, may lead to discrimination based on genetic information. (Sc)"
Thus, the attitudes required to live with science and technology, as well as the benefits and concerns that gene technology brings, were described in the textbooks. Some descriptions regarded genetic medicine; however, the content was marked by concerns. Category 4 accounted for 11.5% of the total, with a high volume of descriptions of Japanese and technology (Table 3).

Discussion
This study revealed that fundamental information related to genetic counseling is taught in compulsory education. They were described not only in science and health and physical education but also in various subjects, such as Japanese, social studies, technology and home economics, and morality (Table 1). In particular, the proportion of description was high in social studies (civics) and technology, which are closely related to life and society (MEXT 2017a; MEXT 2017b). The description was found in the textbooks of Japanese and morality of multiple grades, and the volume of description was relatively large (MEXT 2017c;MEXT 2017d). In this way, by evaluating the proportion of descriptions by textbook (Table 1), we can understand the priority of knowledge related to genetic counseling in each textbook.
From the volume of description by category as presented in Table 3, we can overview the characteristics of each subject. When a textbook directly contains each topic as a theme, the amount of description tends to increase. In contrast, the object description was included as fragmentary knowledge in the textbook when its amount was small. Consequently, knowledge related to genetic counseling was directly or indirectly embedded in various textbooks in compulsory education programs, according to the courses of study.

Information discussed in genetic counseling (direct knowledge)
The generated categories were classified into "Information discussed in genetic counseling (direct knowledge)" and "Fundamental knowledge related to genetic counseling (indirect knowledge)" based on the context of the codes. Direct knowledge directly corresponds to the basic knowledge of clinical genetics (Japanese Board of Medical Genetics and Genomics, Clinical Genetics 2021) and is the fundamental topics of knowledge provided in genetic counseling. Five categories, subcategory 1 (sexual reproduction), subcategory 2 (mitosis and meiosis), subcategory 3 (Mendelian inheritance), subcategory 6 (disease causation), and subcategory 7 (cancer development, causation, and risk factors) were classified into direct knowledge. Indirect knowledge (as described in the "Fundamental knowledge related to genetic counseling (indirect knowledge)" section) is indirectly related to genetic counseling. All subcategories not included in direct knowledge were classified into indirect knowledge. For example, subcategory 4 (biological evolution and diversity) was classified into indirect knowledge because the content was not directly related to genetic counseling (see Supplementary Table 2 for the detailed code). Clinical genetics is a specialized field of academic study for medical professionals who provide genetic counseling; however, it also includes knowledge that is useful for the general public who can be the clients of genetic counseling. The knowledge provided by compulsory education is the fundamental knowledge of the general public. It is useful for clinical genetics professionals to understand the level of the public's knowledge of clinical genetics as a common language for initiating genetic counseling, so that they can provide genetic information considering the client's level of understanding. Therefore, we focused on the gaps between the genetic knowledge taught in compulsory education and the knowledge provided in genetic counseling, and then discussed the topics covered in genetic counseling. Using this method, we could provide adequate genetic counseling information, considering the client's knowledge.

Mendelian law
The textbook for the third year of lower secondary school science covered Mendelian inheritance and explained the law of dominance and the law of segregation in Mendelian laws (subcategory 3). From this description, we can assume that it is possible to learn about the relationship between genotype and phenotype, which is the basic concept of clinical genetics (Bruce and Mira 2013;Robert et al. 2016). However, the textbooks used the term "gene combinations and traits" instead of "genotype and phenotype" (subcategory 3; Supplementary Table 2); therefore, clinical genetics professionals have to select the terms carefully. Furthermore, the textbooks did not explain the "law of independence" in Mendelian law, which states that the inheritance of different genes is independent to each other (Japanese Board of Medical Genetics and Genomics, Clinical Genetics 2021). Without learning this, clients may misunderstand that they have inherited the majority of genes from one parent who appears similar in appearance (Ikeuchi 2015). Clinical genetics professionals should explain that "there is no correlation in the inheritance of traits between genes on different chromosomes." Finally, the explanation of variants was only limited to de novo mutations (subcategory 3). A variant is the difference in DNA sequences between individuals (Bruce and Mira 2013; Japanese Board of Medical Genetics and Genomics, Clinical Genetics 2021). This concept is essential for understanding that genetic medicine is based on relationships between genotype and phenotype (Bruce and Mira 2013). Moreover, genetics is a science about heredity and variation (Brooks 1906). In this sense, variants are crucial in that they are the evidence of diversity. In genetic counseling, it is important to carefully explain that "everyone has variants that are not extraordinary." Other important knowledge related to Mendelian inheritance, such as "human inheritance," "gonadal mosaic," and "mechanisms of genetic disease development" (Japanese Board of Medical Genetics and Genomics, Clinical Genetics 2021), are not covered in compulsory education (subcategory 3). These are necessary to understand the causes of disease and probability of inheritance. However, they have many patterns for each disease, and it is not easy to add them to the courses of study defined by MEXT. They are essential knowledge for clients to correctly recognize and understand genetic contribution to disease. Therefore, these mechanisms must be carefully explained in genetic counseling. Multifactorial genetic diseases, which represent the majority of human diseases, cannot be only explained by Mendelian laws because they are influenced by environmental factors and modifier genes (Bruce and Mira 2013;Robert et al. 2016). Without this assumption, there is a possibility that clients may misunderstand that phenotype depends only on genetic information. Clinical genetics professionals should bear this in mind during genetic counseling.

Mitosis and meiosis (somatic cell and germ cell division)
The science textbook for the third year of lower secondary school covered the mechanism of sexual reproduction (subcategory 1) and mitosis and meiosis (subcategory 2). Understanding these mechanisms is fundamental to understanding chromosome aberrations and differences between germline variants and somatic cell variants. Moreover, it clarifies how genetic information is inherited from parent to child through sexual reproduction (Bruce and Mira 2013;Robert et al. 2016; Japanese Board of Medical Genetics and Genomics, Clinical Genetics 2021). A review on genetic education published in 2015 pointed out that meiosis and genetics were described in different chapters in textbooks based on previous courses of study (Ikeuchi 2015). However, after revision of the courses of study in 2017, these topics were described in the same chapter "Continuation of life" (MEXT 2017e). Therefore, in current compulsory education, it is possible to systematically learn that chromosomes transmit genetic information based on Mendelian law during cell division. Clinical genetics professionals should know that clients have learned the transmission of genetic information in this way.

Disease causation
In a textbook for health and physical education in lower secondary school, it was explained that diseases are caused by the interaction of individual and environmental factors. The individual factors include age, sex, immunity, and heredity (constitution), as well as those acquired after birth that can be controlled by each individual, such as exercise, diet, rest, and sleep (subcategory 6). However, in clinical genetics, all factors except for genetic factors such as gender and constitution are considered environmental factors in principle (Robert et al. 2016). Therefore, the term "environmental factors" in clinical genetics has a different meaning in compulsory education. Most diseases are caused by the interaction of genetic and environmental factors (Bruce and Mira B. Irons 2013;Robert 2016). To conduct appropriate prevention and surveillance of the disease, clients should recognize their own risk based on the correct understanding of both disease factors (Robert et al. 2016;National Comprehensive Cancer Network 2022). In genetic counseling, the definition of the term "environmental factors" requires clarification.

Cancer development and causation
In a textbook for health and physical education in lower secondary school, it is explained that cancer is primarily caused by lifestyle factors (individual factors as described above), such as smoking, drinking, diet, and environmental factors (bacterial and viral infections). They also explained the importance of cancer screening, early detection, and early treatment (subcategory 7). However, there was no mention of genetics, such as "the relationship between heredity and cancer" or "surveillance for hereditary cancers." Although such explanations (lifestyle factors cause cancer) are useful to encourage cancer prevention, explanations that solely rely on environmental factors without genetic factors may make patients feel guilty. In genetic counseling, it is necessary to carefully explain the difference between sporadic cancer and hereditary tumors, and the difference between regular cancer screening and surveillance for hereditary cancer.

Fundamental knowledge related to genetic counseling (indirect knowledge)
Next, we discussed fundamental knowledge related to genetic counseling. This study revealed that not only genetic knowledge, which is provided in genetic counseling, but also various fundamental knowledge related to genetic counseling is transmitted in compulsory education. All subcategories excluded from direct knowledge (described in the "Information discussed in genetic counseling (direct knowledge)" section) were classified into indirect knowledge. Therefore, clinical genetics professionals may be able to provide genetic information using the client's knowledge. The specific idea to be used is described by each subcategory.

Biological diversity and individual differences at the DNA level
Biological evolution and diversity (subcategory 4) and individual differences at the DNA level (subcategory 5) may improve the understanding of "genotype and phenotype" and "genetic variants and diversity." For example, when clinical genetics professionals inform clients that a "genetic variant is not extraordinary (the "Mendelian law" section)," they can use the client's initial knowledge to explain the following: "Diverse species were originally branched from a single species by mutation accumulation. In other words, everyone has mutations. Therefore, each person has a different genetic constitution; for example, the side effects of certain medications will appear only in some individuals, and different individuals will have varying abilities to metabolize alcohol."

Juvenile and congenital diseases
The textbook also covered several human diseases. These included diseases that develop at a young age and congenital diseases, such as osteosarcoma, neuroblastoma, congenital visual impairment, congenital heart disease, and leukemia. They are primarily included in morality and were described as features of characters in the stories (subcategory 8; Supplementary Table 2). Congenital diseases often depend on genetic factors in their development (Japanese Board of Medical Genetics and Genomics, Clinical Genetics 2021). Therefore, congenital diseases had represented the majority of diseases discussed in genetic counseling and are still considered one of the primary fields (Uhlmann et al. 2009;Japanese Board of Medical Genetics and Genomics, Clinical Genetics 2021). Most congenital diseases are rare. Thus, clients often have difficulty in visualizing the disease. However, as the previously mentioned diseases appear in compulsory education, it may be relatively easier to imagine the disease and its impact on the patient's life. Understanding the types of commonly known juvenile and congenital diseases is expected to be supportive in genetic counseling.

Realization of a harmonious society
Regarding efforts and barriers to the realization of a harmonious society (category 3), there was a specific explanation regarding the measures for the harmonious society. The content may support the concept of clinical genetics, stating that "diseases, pathologies, and genotypes based on genetic variants (mutations) are not the exception but human diversity. People should respect their diversity and uniqueness (Japanese Board of Medical Genetics and Genomics, Clinical Genetics 2021)." When clinical genetics professionals discuss the diversity of genetic information, they may use the client's knowledge in the following way: "Respect for diversity and social resources are important so that everyone can live comfortably regardless of illness or disability. The same is true for genetic diseases. Genetic information should be understood as diversity where personalized medicine and social resources would be realized."

Scientific technology and human evolution
An important message in scientific technology and human evolution (subcategory 14) states that we should not forget compassion for others when utilizing technology. This is also connected to the way we think about the use of technology around us. For example, germline genome editing is expected to facilitate the treatment of untreatable genetic diseases; however, there are concerns about the safety and ethical aspects of the technology, and the clinical application of the technology is controversial in Japan. However, genome editing may soon be applied clinically. The National Academy of Sciences announced in 2017 that genome editing of human fertilized eggs had been approved only in cases of serious diseases (National Academies of Sciences, Engineering, and Medicine et al. 2017). In some institutions, genome editing, which is promising treatment for hereditary diseases, is already discussed in genetic counseling sessions for untreatable diseases (Taguchi et al. 2019). The thought process surrounding new technologies may provide other avenues for the management of genetic information. Therefore, clients' learning strategies should be considered during genetic counseling.

Benefits and concerns of gene technology
In benefits and concerns of gene technology (subcategory 15), some examples were presented where gene technology is applied to real life. These may improve the understanding of genetics or build familiarity with gene technology. However, few benefits and more concerns were described regarding genetic medicine. The goals of medical genetics are the diagnosis, treatment, and prevention of hereditary disorders (Wertz et al. 1995). The field of genetic medicine is constantly expanding and has become relevant to everyone. For everyone to receive genetic medicine realized by gene technology with peace of mind, it is necessary to convey legitimate genetic medical information in a well-balanced manner rather than only emphasizing concerns.
Because people understand things based on prior knowledge and experience, the knowledge taught in compulsory education is helpful as the fundamental knowledge for understanding the genetic issues that people will face in the future. Boerwinkel et al. (2017) proposed genetic literacy required in the twenty-first century. In terms of their framework, three of the nine conceptual knowledge were included in the textbook (subcategory 2 and subcategory 3). As for the sociocultural knowledge, the topics of genetic modification technology, iPS cells, and genetic diagnosis were covered in textbook (subcategory 15), although there is room for improvement in the description of risk benefit. Epistemic knowledge was not included. As discussed in previous sections, people can learn the fundamental knowledge related to clinical genetics; however, they were not sufficient to recognize the genetic contributions to disease for making decision. Therefore, it is important to provide information in a way that considers the baseline knowledge of the client, which is the fundamental knowledge revealed in this study. The contents of textbooks do not change rapidly, and it is presumed that many Japanese people are given knowledge with similar characteristics. The changes in textbooks over time reflect the changes in society. Therefore, the fundamental knowledge acquired in compulsory education may be updated by subsequent social life, and the fundamental knowledge of adults who received compulsory education in the past may have similar characteristics to the fundamental knowledge of compulsory education in the present day. The present study analyzed both qualitative and quantitative data to research the contents taught in Japanese compulsory education.

Strengths, limitations, and perspectives
This study has three strengths. First, this study is unique in that it did not aim to improve genetic education as in previous textbook surveys but rather attempted to understand the characteristics of knowledge taught in compulsory education and to provide better support in genetic counseling. Second, to realize the first point, we surveyed textbooks including general subjects (Japanese or social studies) and not just those pertaining to science and health. Third, we used the official textbook for clinical geneticists as a conceptual framework and explored paraphrased statements and even the content derived from them. This approach ensured the reliability of the analysis and made it possible to identify content that was difficult to extract owing to differences in the level of compulsory education for all citizens and clinical genetics for clinical geneticists. However, our study also has several limitations. This study focused on the knowledge that was taught in compulsory education. To determine the baseline knowledge of the general public, additional studies, including questionnaires or surveys, should be included. We investigated only the commonly used textbooks as of 2021. A longitudinal study by year of publication is needed to understand educational change over time, and a comparative study between publishers is required to observe differences between textbooks of the same grade and subject. Teaching genetic knowledge is important in compulsory education, which aims not only to acquire basic and fundamental knowledge but also to improve the ability to think or make decisions. This study revealed that a certain amount of genetic knowledge and fundamental knowledge related to genetic counseling are taught in compulsory education. We believe that better genetic counseling can be achieved by using the results of this study. However, in future, it is possible that greater quality genetic counseling may be achieved by improving the content of genetics taught in compulsory education.

Conclusions
All people can face problems related to genetics and become a client of genetic counseling. To improve genetic counseling, it is important for clinical genetics professionals to understand the fundamental knowledge of clients, which is established based on compulsory education. It was revealed that various fundamental knowledge related to genetic counseling was taught in compulsory education. This information may contribute to effective genetic counseling.
Author contribution Eri Sakai conceptualized and designed the study, conducted the acquisition, analyses, and interpretation of data, drafted the initial manuscript, and reviewed and revised the manuscript. Takahiro Yamada conceptualized and designed the study, conducted the acquisition, analyses, and interpretation of data, drafted the initial manuscript, and reviewed and revised the manuscript. Tomomi Funaki contributed to study design and data analyses. Miho Iwakuma designed the study, contributed to data analyses, and critically reviewed and revised the manuscript. Harumo Osawa contributed to the acquisition and analyses of the data. Kana Morimoto contributed to the acquisition and analyses of the data. Shinji Kosugi contributed to the analyses and interpretation of the data, and critically reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Declarations
This article does not contain any studies of human or animal subjects performed by the any of the authors.

Competing interests
The authors declare no competing interests.