HUMAN MUTATION 21:146^150 (2003)
DATABASES
The Iranian Human Mutation Gene Bank:
A Data and Sample Resource for Worldwide
Collaborative Genetics Research
Hossein Najmabadin, Maryam Neishabury, Farhad Sahebjam, Kimia Kahrizi, Yousef Shafaghati,
Nushin Nikzat, Maryam Jalalvand, Farahnaz Aminy, Susan Bany Hashemi, Babak Moghimi, Ali Reza
Noorian, Ali Jannati, Mehrdad Mohammadi, and Khalil Javan
Genetics Research Center, Social Welfare and Rehabilitation Sciences University, Tehran, Iran
Communicated by Mark H. Paalman
As Human Genome Project exploration continues, the necessity of having a broader spectrum of genomic
DNA material from different nationalities to study various aspects of hereditary disease becomes more
obvious. The existence of high genetic polymorphism within and between different communities in the
world makes it necessary for the gene hunters to investigate many different populations. Iran, a large
country with close to 66 million people, is a land of different nationalities, tribes, and religions that offers
a highly heterogeneous gene pool to the genetics researcher. The purity of many different races in this
country has been highly conserved by geographical borders and by an ancient culture that has always
encouraged intrafamilial marriages. All these have created a population that is remarkably heterogeneous
yet high in consanguinity rate. During the last five years of investigation we have established a DNA
bank, the Iranian Human Mutation Gene Bank (www.IHMGB.com), which contains all genetic diseases
studied in Iran that have the Mendelian mode of inheritance. Some of the samples are assigned to
common or novel mutations and others belong to patients with clinical profiles associated with particular
genetic diseases but undefined mutation. This bank stores samples of DNA from the patient and his/her
first-degree relatives together with a comprehensive pedigree and clinical profile for each sample. To
facilitate collaboration with other scientists around the world with the same interests, we decided to
present our experimental projects online. This DNA bank provides opportunities for us to collaborate
with scientists outside Iran. It offers a sample resource to research scientists around the world, at no
charge, for the purpose of investigating the various aspects of genetic disorders from prenatal diagnosis to
gene structure and function. It is strongly stressed that no commercial benefit is involved in the
establishment of this DNA bank and the DNA samples are free of charge. However, to meet our goals and
to respect ethical values, DNA samples can only be used under certain conditions stated in the User
Consent Form. Hum Mutat 21:146–150, 2003. r 2003 Wiley-Liss, Inc.
KEY WORDS: database; mutation bank; genetic; polymorphism; Iranian; DNA bank
DATABASES:
www.IHMGB.com (Iranian Human Mutation Gene Bank)
INTRODUCTION of the Iranian population to this research, we have
established a DNA bank. This article reviews our
The completion of the Human Genome Project primary aims and structure, and the facilities present
takes us to a new era in clinical genetics, where in this bank.
identifying the new genes responsible for hereditary
diseases and their location and function becomes
the next major challenge in understanding the Received 6 September 2002; accepted revised manuscript
mechanism of disease formation. Hopefully, the 31 October 2002.
n
cure for these hereditary diseases will soon follow. Correspondence to: Hossein Najmabadi, Genetics Research
Center, Social Welfare and Rehabilitation Sciences University,
The existence of high genetic polymorphism within Tehran, Iran. E-mail:
and between different communities in the world DOI:10.1002/humu.10164
makes it necessary for gene hunters to investigate Published online in Wiley InterScience (www.interscience.wiley.
many different populations. To realize the contribution com).
r2003 WILEY-LISS, INC.
, IRANIAN HUMAN GENE BANK 147
TABLE 1. Ethnic Groups andTheir PercentageWithin Mahboudi et al., 1996; Merat et al., 1993]. The
the Iranian Population known beta thalassemia gene mutations have Medi-
Ethnic group % of the total population terranean, Indian, Kurdish, Turkish, Arabic, African,
Chinese, and Afro-American origin. In addition, a
Persian 51%
Azeri 24% haplotype analysis shows different haplotypes between
Gilaki and Mazandarani 8% the European and Iranian IVSII-1 mutation.
Kurd 7% Autosomal recessive non-syndromic sensoneural
Arab 3%
Lur 2%
deafness (ARNSD) is the most common form of
Baloochi 2% severe inherited hearing loss [Reardon, 1992]. It
Turkmen 2% is an extremely heterogeneous disorder in which
Other 1% at least 30 reported loci [Van Camp et al., 1997;
Zbar et al., 1998; Keats and Berlin, 1999] and
mutations in one gene (GJB2) have been shown
Heterogeneous Gene Pool As Well As Consanguinity to be major cause of ARNSD in many different
populations [Maw et al., 1995; Gasparini et al., 1997;
Iran, a large country with different ethnic groups,
Kelsell et al., 1997; Park et al., 2000; Morell et al.,
tribes, and religions and a population of close to 66
1998; Zelante et al., 1997]. We have studied the
million, offers a highly heterogeneous gene pool to the
mutation load of GJB2 in the Iranian population and
research in genetics. Iran’s enormous diversity of
have found the prevalence to be much lower than in
ethnic types creates a lasting impression on every
other studied populations (Najmabadi et al., 2001;
person who first visits this country. The ethnic groups
submitted manuscript). These differences reflect the
we focus on are summarized in Table 1; each group has
non-founder effects for the most common deafness-
its own specific history, culture, costume, and
causing GJB2 allele variant, the 35delG mutation.
language. The historical background and anthropolo-
Our data suggest that the mutation load for the
gical origin of these groups have been studied in great
other known deafness-causing genes will be specific
detail. However, researchers are not unanimous about
to the Iranian population and cannot be extrapolated
the origin of these people. Long-time wars with foreign
from other populations. We also expect that some
nations, immigration from the neighboring countries,
unknown genes make a contribution to inherited
a location on the route of the Silk Road, and the new
deafness in Iran.
style of modern life have influenced the shape of the
Iranian people a great deal, making it even more
diverse. Yet, the purity of many different races in this DNA BANK
country has been conserved within geographical
To improve our diagnostics and to be able to
borders and by an ancient culture that has always
contribute to basic research in genetic diseases
encouraged intrafamilial marriages. All of these factors
common throughout the world, we found it essential
have created a population that is remarkably hetero-
to make use of the heterogeneity of our population.
geneous and yet high in consanguinity rate.
Our primary aim was prevention of hereditary
diseases, as well as possible future treatments. Our
New Mutations; Rare and New Genes
DNA bank is a collection of reserved DNA samples
The outcome of two projects on beta thalassemia from all genetic diseases passed on by the Mendelian
and non-syndromic deafness [Najmabadi et al., 2001; mode of inheritance. The list of these disorders is
Najmabadi et al., 2002a] clearly shows the importance shown in Table 2. Only a few of these disorders have
of studying this population for the purpose of been the subject of molecular genetics investigations,
determining new mutations or new genes involved including thalassemia, deafness, male infertility, and
in these two globally prevalent diseases. Beta- some musculoskeletal disorders. We hope that this
thalassemia, the most common genetic disorder in collection will be a valuable study tool for future
Iran, has been more extensively studied. An investi- research projects aimed at preventing further inci-
gation to determine the spectrum of 15 known beta- dence of hereditary diseases by carrier detection and
globin gene mutations in eight different geographical prenatal diagnosis, and for those projects aimed at
areas in Iran has shown how this spectrum greatly aiding in the early detection or cure in affected
differs from region to region (Fig. 1) [Najmabadi et al., patients. This gene bank could also provide a valuable
2001]. Another recent study using the Iranian sample resource for other scientists working on various
population [Najmabadi et al., 2002b] has added 25 aspects of genetic disorders, such as new genes, new
more mutations to this spectrum some of them rare mutations, structure and function of the genes
and some new, and yet the beta globin gene muta- involved in genetic disorders, and polymorphisms.
tions for about 10% of the population still remain This DNA bank also contains normal DNA samples
unknown. Other investigators have reported similar that can aid in the study of polymorphisms in our
findings [Nozari et al., 1995; Noori-Daloii et al., 1994a,b; population.
DATABASES
The Iranian Human Mutation Gene Bank:
A Data and Sample Resource for Worldwide
Collaborative Genetics Research
Hossein Najmabadin, Maryam Neishabury, Farhad Sahebjam, Kimia Kahrizi, Yousef Shafaghati,
Nushin Nikzat, Maryam Jalalvand, Farahnaz Aminy, Susan Bany Hashemi, Babak Moghimi, Ali Reza
Noorian, Ali Jannati, Mehrdad Mohammadi, and Khalil Javan
Genetics Research Center, Social Welfare and Rehabilitation Sciences University, Tehran, Iran
Communicated by Mark H. Paalman
As Human Genome Project exploration continues, the necessity of having a broader spectrum of genomic
DNA material from different nationalities to study various aspects of hereditary disease becomes more
obvious. The existence of high genetic polymorphism within and between different communities in the
world makes it necessary for the gene hunters to investigate many different populations. Iran, a large
country with close to 66 million people, is a land of different nationalities, tribes, and religions that offers
a highly heterogeneous gene pool to the genetics researcher. The purity of many different races in this
country has been highly conserved by geographical borders and by an ancient culture that has always
encouraged intrafamilial marriages. All these have created a population that is remarkably heterogeneous
yet high in consanguinity rate. During the last five years of investigation we have established a DNA
bank, the Iranian Human Mutation Gene Bank (www.IHMGB.com), which contains all genetic diseases
studied in Iran that have the Mendelian mode of inheritance. Some of the samples are assigned to
common or novel mutations and others belong to patients with clinical profiles associated with particular
genetic diseases but undefined mutation. This bank stores samples of DNA from the patient and his/her
first-degree relatives together with a comprehensive pedigree and clinical profile for each sample. To
facilitate collaboration with other scientists around the world with the same interests, we decided to
present our experimental projects online. This DNA bank provides opportunities for us to collaborate
with scientists outside Iran. It offers a sample resource to research scientists around the world, at no
charge, for the purpose of investigating the various aspects of genetic disorders from prenatal diagnosis to
gene structure and function. It is strongly stressed that no commercial benefit is involved in the
establishment of this DNA bank and the DNA samples are free of charge. However, to meet our goals and
to respect ethical values, DNA samples can only be used under certain conditions stated in the User
Consent Form. Hum Mutat 21:146–150, 2003. r 2003 Wiley-Liss, Inc.
KEY WORDS: database; mutation bank; genetic; polymorphism; Iranian; DNA bank
DATABASES:
www.IHMGB.com (Iranian Human Mutation Gene Bank)
INTRODUCTION of the Iranian population to this research, we have
established a DNA bank. This article reviews our
The completion of the Human Genome Project primary aims and structure, and the facilities present
takes us to a new era in clinical genetics, where in this bank.
identifying the new genes responsible for hereditary
diseases and their location and function becomes
the next major challenge in understanding the Received 6 September 2002; accepted revised manuscript
mechanism of disease formation. Hopefully, the 31 October 2002.
n
cure for these hereditary diseases will soon follow. Correspondence to: Hossein Najmabadi, Genetics Research
Center, Social Welfare and Rehabilitation Sciences University,
The existence of high genetic polymorphism within Tehran, Iran. E-mail:
and between different communities in the world DOI:10.1002/humu.10164
makes it necessary for gene hunters to investigate Published online in Wiley InterScience (www.interscience.wiley.
many different populations. To realize the contribution com).
r2003 WILEY-LISS, INC.
, IRANIAN HUMAN GENE BANK 147
TABLE 1. Ethnic Groups andTheir PercentageWithin Mahboudi et al., 1996; Merat et al., 1993]. The
the Iranian Population known beta thalassemia gene mutations have Medi-
Ethnic group % of the total population terranean, Indian, Kurdish, Turkish, Arabic, African,
Chinese, and Afro-American origin. In addition, a
Persian 51%
Azeri 24% haplotype analysis shows different haplotypes between
Gilaki and Mazandarani 8% the European and Iranian IVSII-1 mutation.
Kurd 7% Autosomal recessive non-syndromic sensoneural
Arab 3%
Lur 2%
deafness (ARNSD) is the most common form of
Baloochi 2% severe inherited hearing loss [Reardon, 1992]. It
Turkmen 2% is an extremely heterogeneous disorder in which
Other 1% at least 30 reported loci [Van Camp et al., 1997;
Zbar et al., 1998; Keats and Berlin, 1999] and
mutations in one gene (GJB2) have been shown
Heterogeneous Gene Pool As Well As Consanguinity to be major cause of ARNSD in many different
populations [Maw et al., 1995; Gasparini et al., 1997;
Iran, a large country with different ethnic groups,
Kelsell et al., 1997; Park et al., 2000; Morell et al.,
tribes, and religions and a population of close to 66
1998; Zelante et al., 1997]. We have studied the
million, offers a highly heterogeneous gene pool to the
mutation load of GJB2 in the Iranian population and
research in genetics. Iran’s enormous diversity of
have found the prevalence to be much lower than in
ethnic types creates a lasting impression on every
other studied populations (Najmabadi et al., 2001;
person who first visits this country. The ethnic groups
submitted manuscript). These differences reflect the
we focus on are summarized in Table 1; each group has
non-founder effects for the most common deafness-
its own specific history, culture, costume, and
causing GJB2 allele variant, the 35delG mutation.
language. The historical background and anthropolo-
Our data suggest that the mutation load for the
gical origin of these groups have been studied in great
other known deafness-causing genes will be specific
detail. However, researchers are not unanimous about
to the Iranian population and cannot be extrapolated
the origin of these people. Long-time wars with foreign
from other populations. We also expect that some
nations, immigration from the neighboring countries,
unknown genes make a contribution to inherited
a location on the route of the Silk Road, and the new
deafness in Iran.
style of modern life have influenced the shape of the
Iranian people a great deal, making it even more
diverse. Yet, the purity of many different races in this DNA BANK
country has been conserved within geographical
To improve our diagnostics and to be able to
borders and by an ancient culture that has always
contribute to basic research in genetic diseases
encouraged intrafamilial marriages. All of these factors
common throughout the world, we found it essential
have created a population that is remarkably hetero-
to make use of the heterogeneity of our population.
geneous and yet high in consanguinity rate.
Our primary aim was prevention of hereditary
diseases, as well as possible future treatments. Our
New Mutations; Rare and New Genes
DNA bank is a collection of reserved DNA samples
The outcome of two projects on beta thalassemia from all genetic diseases passed on by the Mendelian
and non-syndromic deafness [Najmabadi et al., 2001; mode of inheritance. The list of these disorders is
Najmabadi et al., 2002a] clearly shows the importance shown in Table 2. Only a few of these disorders have
of studying this population for the purpose of been the subject of molecular genetics investigations,
determining new mutations or new genes involved including thalassemia, deafness, male infertility, and
in these two globally prevalent diseases. Beta- some musculoskeletal disorders. We hope that this
thalassemia, the most common genetic disorder in collection will be a valuable study tool for future
Iran, has been more extensively studied. An investi- research projects aimed at preventing further inci-
gation to determine the spectrum of 15 known beta- dence of hereditary diseases by carrier detection and
globin gene mutations in eight different geographical prenatal diagnosis, and for those projects aimed at
areas in Iran has shown how this spectrum greatly aiding in the early detection or cure in affected
differs from region to region (Fig. 1) [Najmabadi et al., patients. This gene bank could also provide a valuable
2001]. Another recent study using the Iranian sample resource for other scientists working on various
population [Najmabadi et al., 2002b] has added 25 aspects of genetic disorders, such as new genes, new
more mutations to this spectrum some of them rare mutations, structure and function of the genes
and some new, and yet the beta globin gene muta- involved in genetic disorders, and polymorphisms.
tions for about 10% of the population still remain This DNA bank also contains normal DNA samples
unknown. Other investigators have reported similar that can aid in the study of polymorphisms in our
findings [Nozari et al., 1995; Noori-Daloii et al., 1994a,b; population.
