عنوان
پدید آورنده
موضوع
رده
کتابخانه
محل استقرار
شماره کتابشناسی ملی
شماره
TL56850
زبان اثر
زبان متن نوشتاري يا گفتاري و مانند آن
انگلیسی
عنوان و نام پديدآور
عنوان اصلي
Definition of Immunoglobulin Germline Genes by Next Generation Sequencing for Studies of Antigen-Specific B Cell Responses
نام عام مواد
[Thesis]
نام نخستين پديدآور
Vázquez Bernat, Néstor
نام ساير پديدآوران
Karlsson Hedestam, Gunilla B.
وضعیت نشر و پخش و غیره
نام ناشر، پخش کننده و غيره
Karolinska Institutet (Sweden)
تاریخ نشرو بخش و غیره
2019
يادداشت کلی
متن يادداشت
67 p.
یادداشتهای مربوط به پایان نامه ها
جزئيات پايان نامه و نوع درجه آن
Ph.D.
کسي که مدرک را اعطا کرده
Karolinska Institutet (Sweden)
امتياز متن
2019
یادداشتهای مربوط به خلاصه یا چکیده
متن يادداشت
Immunoglobulins play a critical role in the adaptive immune system, existing as cell surface-expressed B cell receptors and secreted antibodies. Circulating antibodies are the main correlate of protective immunity for most vaccines. An improved understanding of the germline genes that rearrange to encode the vast repertoire of antibodies is therefore of central interest. Despite this, current databases of immunoglobulin germline gene variation are incomplete, both for humans and research animal models, limiting studies of antigen-specific B cell responses. In Paper I, we developed a computational tool, IgDiscover, which infers germline immunoglobulin V alleles from the repertoire of expressed antibodies in a given individual. We validated IgDiscover for the identification of human, mouse and rhesus macaque IGHV alleles and described novel IGHV alleles in all three species. Our results highlighted a high degree of inter-individual allelic diversity in rhesus macaques. In Paper II, we optimized and compared two major immunoglobulin library production methods based on 5'RACE and 5'multiplex PCR, respectively. We observed that, despite 5'RACE being unbiased in terms of amplification and having the advantage of not requiring 5' end IGHV genomic information, current limitations on high-throughput sequence read length resulted in the 5' multiplex method delivering a higher quality output due to its shorter amplicon size. In Paper III, we inferred germline immunoglobulin alleles in 45 macaques from four sub-populations of the two most common species used in biomedical research, rhesus and cynomolgus macaques. We confirmed and extended our observations concerning high inter-individual diversity, demonstrating that it was highest among Indonesian cynomolgus macaques and lowest among Mauritian cynomolgus macaques in the sub-populations studied. We compiled comprehensive IGHV, D and J allele databases and used several methods to independently validate novel alleles. In conclusion, the work presented in this thesis establishes a road map to generate individualized immunoglobulin germline gene databases from diverse species, even if genomic immunoglobulin loci information is limited. This thesis also examines the advantages and disadvantages of commonly used next generation sequencing library preparation methods. Finally, it reports novel inferred immunoglobulin alleles in humans and macaques and illustrates a high degree of inter-individual immunoglobulin allelic diversity in primates, underlining the utility of generating individualized immunoglobulin databases for studies of immune repertoires.
اصطلاحهای موضوعی کنترل نشده
اصطلاح موضوعی
Cellular biology
اصطلاح موضوعی
Genetics
اصطلاح موضوعی
Immunology
اصطلاح موضوعی
Pharmaceutical sciences
اصطلاح موضوعی
Public health
اصطلاح موضوعی
Virology
نام شخص به منزله سر شناسه - (مسئولیت معنوی درجه اول )
مستند نام اشخاص تاييد نشده
Vázquez Bernat, Néstor
نام شخص - ( مسئولیت معنوی درجه دوم )
مستند نام اشخاص تاييد نشده
Karlsson Hedestam, Gunilla B.
شناسه افزوده (تنالگان)
مستند نام تنالگان تاييد نشده
Karolinska Institutet (Sweden)
دسترسی و محل الکترونیکی
نام الکترونيکي
مطالعه متن کتاب وضعیت انتشار
فرمت انتشار
p
اطلاعات رکورد کتابشناسی
نوع ماده
[Thesis]
کد کاربرگه
276903
اطلاعات دسترسی رکورد
سطح دسترسي
a
تكميل شده
Y
