Genetics Commons^™

Electrotransfer Of Different Control Plasmids Elicits Different Antitumor Effectiveness In B16.F10 Melanoma, Masa Bosnjak, Tanjo Jesenko, Urska Kamensek, Gregor Sersa, Jaka Lavrencak, Loree Heller, Maja Cemazar

Bioelectrics Publications

Several studies have shown that different control plasmids may cause antitumor action in different murine tumor models after gene electrotransfer (GET). Due to the differences in GET protocols, plasmid vectors, and experimental models, the observed antitumor effects were incomparable. Therefore, the current study was conducted comparing antitumor effectiveness of three different control plasmids using the same GET parameters. We followed cytotoxicity in vitro and the antitumor effect in vivo after GET of control plasmids pControl, pENTR/U6 scr and pVAX1 in B16.F10 murine melanoma cells and tumors. Types of cell death and upregulation of selected cytosolic DNA sensors and cytokines were …

Role Of Sex Chromosomes In Sexual Dimorphism Of Angii-Induced Abdominal Aortic Aneurysms, Yasir Alsiraj

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal aortic aneurysms (AAAs), a permanent dilation in the abdominal region of the aorta, is a highly sexually dimorphic disease. AAAs prevalence is ranging from 4-10 fold higher in males than females. Defining the mechanistic basis for reduced (in females) or increased (in males) AAA formation and progression may uncover potential therapeutic targets. The majority of studies examining sexual dimorphism focus on the role of sex hormones. However, genes residing on sex chromosomes, in addition to sex hormones, may contribute to sexual dimorphism of AAAs. For example, the X chromosome contains about 5% of the whole genome, but the role …

Crispr Genetic Editing: Paths For Christian Acceptance And Analysis Of In Vivo And In Vitro Efficiency, Mandeep Sandhu

Scripps Senior Theses

With advancements in CRISPR-cas9 broadening the potential paths for clinical usage of genetic editing, conversations about genetic editing have grown to outside simply scientific communities and into mainstream conversations. This study focuses specifically on Christian discourse of genetic editing and locates four major tensions for many Christians when they think about genetic editing: beginning of life, Creator-human relationship, imago Dei, and stewardship. With these major concerns in mind, I identify epigenetics, somatic cell genetic editing, and in vivo genetic editing research as important research paths to pursue as they can potentially produce techniques that more Christian individuals would feel comfortable …

Wild-Type P53 Enhances Endothelial Barrier Function By Mediating Rac1 Signalling And Rhoa Inhibition, Nektarios Barabutis, Christiana Dimitropoulou, Betsy Gregory, John D. Catravas

Bioelectrics Publications

Inflammation is the major cause of endothelial barrier hyper-permeability, associated with acute lung injury and acute respiratory distress syndrome. This study reports that p53 "orchestrates" the defence of vascular endothelium against LPS, by mediating the opposing actions of Rac1 and RhoA in pulmonary tissues. Human lung microvascular endothelial cells treated with HSP90 inhibitors activated both Rac1- and P21-activated kinase, which is an essential element of vascular barrier function. 17AAG increased the phosphorylation of both LIMK and cofilin, in contrast to LPS which counteracted those effects. Mouse lung microvascular endothelial cells exposed to LPS exhibited decreased expression of phospho-cofilin. 17AAG treatment …

The Ability Of Different Imputation Methods To Preserve The Significant Genes And Pathways In Cancer, Rosa Aghdam, Taban Baghfalaki, Pegah Khosravi, Elnaz Saberi Ansari

Publications and Research

Deciphering important genes and pathways from incomplete gene expression data could facilitate a better understanding of cancer. Different imputation methods can be applied to estimate the missing values. In our study, we evaluated various imputation methods for their performance in preserving significant genes and pathways. In the first step, 5% genes are considered in random for two types of ignorable and non-ignorable missingness mechanisms with various missing rates. Next, 10 well-known imputation methods were applied to the complete datasets. The significance analysis of microarrays (SAM) method was applied to detect the significant genes in rectal and lung cancers to showcase …

Ran Translation At C9orf72-Associated Repeat Expansions Is Selectively Enhanced By The Integrated Stress Response, Katelyn M. Green, M. Rebecca Glineburg, Michael G. Kearse, Brittany N. Flores, Alexander E. Linsalata, Stephen J. Fedak, Aaron C. Goldstrohm, Sami J. Barmada, Peter K. Todd

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Repeat-associated non-AUG (RAN) translation allows for unconventional initiation at disease-causing repeat expansions. As RAN translation contributes to pathogenesis in multiple neurodegenerative disorders, determining its mechanistic underpinnings may inform therapeutic development. Here we analyze RAN translation at G₄C₂ repeat expansions that cause C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9RAN) and at CGG repeats that cause fragile X-associated tremor/ataxia syndrome. We find that C9RAN translation initiates through a cap- and eIF4A-dependent mechanism that utilizes a CUG start codon. C9RAN and CGG RAN are both selectively enhanced by integrated stress response (ISR) activation. ISR-enhanced RAN translation requires an …

Validation Of Minimally-Invasive Sample Collection Methods For Measurement Of Telomere Length, Stephanie A. Stout, Jue Lin, Natalie Hernandez, Elysia Poggi Davis, Elizabeth Blackburn, Judith E. Carroll, Laura M. Glynn

Psychology: Faculty Scholarship

Objective: The discovery of telomere length (TL) as a biomarker of cellular aging and correlate of age-related disease has generated a new field of research in the biology of healthy aging. Although the most common method of sample collection for TL is venous blood draw, less-invasive DNA collection methods are becoming more widely used. However, how TL relates across tissues derived from these sample collection methods is poorly understood. The current study is the first to characterize the associations in TL across three sample collection methods: venous whole blood, finger prick dried blood spot and saliva.

Methods: TL …

Analysis Of Diagnostic, Preventive, And Disease-Modifying Therapeutic Measures Of Alzheimer’S Disease, Ghazal Habib Havoutis

HCNSO Student Capstones

Alzheimer’s disease (AD) is the most common late-onset neurodegenerative disorder and cause of dementia, characterized by the formation of neurofibrillary tangles and senile plaque deposits. The heterogeneous nature of the disease (both genetically and environmentally) makes it difficult to prevent or cure. Without prevention, the prevalence of AD is expected to triple by 2050. However, because the diagnosis of AD is usually preceded by years of cognitive impairment, early detection may aid in reducing prevalence. Thus, there is a need for validated diagnostic measures for early and improved diagnosis and prevention. In this review, current and ongoing classifiers of early …

Quality Of Life: Socio-Demographic And Genetic Determinants As Well As Links With Cancer Outcomes, Jeanne Pierzynski

Dissertations and Theses (Open Access)

Quality of life (QOL) is an independent prognostic factor for cancer. Lung cancer is the leading cause of cancer death. Breast cancer is the most diagnosed. Bladder cancer is the most expensive cancer to treat because of its high recurrence rate. We set to perform comprehensive analyses of predictors of QOL in these cancer sites with the future goal of improving QOL and outcomes.

In 6,456 newly diagnosed lung cancer patients, we investigated the relationship between baseline patient characteristics and QOL to identify determinants of QOL. A QOL questionnaire (SF-12v1) measured patients’ physical component summary (PCS) and mental component summary …

Genetic Signatures For Helicobacter Pylori Strains Of West African Origin, Kennady K. Bullock, Carrie L. Shaffer, Andrew W. Brooks, Ousman Secka, Mark H. Forsyth, Mark S. Mcclain, Timothy L. Cover

Veterinary Science Faculty Publications

Helicobacter pylori is a genetically diverse bacterial species that colonizes the stomach in about half of the human population. Most persons colonized by H. pylori remain asymptomatic, but the presence of this organism is a risk factor for gastric cancer. Multiple populations and subpopulations of H. pylori with distinct geographic distributions are recognized. Genetic differences among these populations might be a factor underlying geographic variation in gastric cancer incidence. Relatively little is known about the genomic features of African H. pylori strains compared to other populations of strains. In this study, we first analyzed the genomes of …

Abnormal Contractility In Human Heart Myofibrils From Patients With Dilated Cardiomyopathy Due To Mutations In Ttn And Contractile Protein Genes, Petr G. Vikhorev, Natalia Smoktunowicz, Alex B. Munster, O'Neal Copeland, Sawa Kostin, Cecile Montgiraud, Andrew E. Messer, Mohammad R. Toliat, Amy Li, Cristobal G. Dos Remedios, Sean Lal, Cheavar A. Blair, Kenneth S. Campbell, Maya E. Guglin, Ralph Knoll, Steven B. Marston

Physiology Faculty Publications

Dilated cardiomyopathy (DCM) is an important cause of heart failure. Single gene mutations in at least 50 genes have been proposed to account for 25–50% of DCM cases and up to 25% of inherited DCM has been attributed to truncating mutations in the sarcomeric structural protein titin (TTNtv). Whilst the primary molecular mechanism of some DCM-associated mutations in the contractile apparatus has been studied in vitro and in transgenic mice, the contractile defect in human heart muscle has not been studied. In this study we isolated cardiac myofibrils from 3 TTNtv mutants, and 3 with contractile protein mutations (TNNI3 …

Pattern Discovery In Brain Imaging Genetics Via Scca Modeling With A Generic Non-Convex Penalty, Lei Du, Kefei Liu, Xiaohui Yao, Jingwen Yan, Shannon L. Risacher, Junwei Han, Lei Guo, Andrew J. Saykin, Li Shen, Michael W. Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, Robert C. Green, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, David Holtzman, Charles D. Smith, Gregory Jicha, Peter A. Hardy, Partha Sinha, Elizabeth Oates, Gary Conrad

Neurology Faculty Publications

Brain imaging genetics intends to uncover associations between genetic markers and neuroimaging quantitative traits. Sparse canonical correlation analysis (SCCA) can discover bi-multivariate associations and select relevant features, and is becoming popular in imaging genetic studies. The L1-norm function is not only convex, but also singular at the origin, which is a necessary condition for sparsity. Thus most SCCA methods impose ℓ₁-norm onto the individual feature or the structure level of features to pursuit corresponding sparsity. However, the ℓ₁-norm penalty over-penalizes large coefficients and may incurs estimation bias. A number of non-convex penalties are proposed to reduce …

Hne-Modified Proteins In Down Syndrome: Involvement In Development Of Alzheimer Disease Neuropathology, Eugenio Barone, Elizabeth Head, D. Allan Butterfield, Marzia Perluigi

Sanders-Brown Center on Aging Faculty Publications

Down syndrome (DS), trisomy of chromosome 21, is the most common genetic form of intellectual disability. The neuropathology of DS involves multiple molecular mechanisms, similar to AD, including the deposition of beta-amyloid (Aβ) into senile plaques and tau hyperphosphorylating in neurofibrillary tangles. Interestingly, many genes encoded by chromosome 21, in addition to being primarily linked to amyloid-beta peptide (Aβ) pathology, are responsible for increased oxidative stress (OS) conditions that also result as a consequence of reduced antioxidant system efficiency. However, redox homeostasis is disturbed by overproduction of Aβ, which accumulates into plaques across the lifespan in DS as well as …

Linking Kindling To Increased Glutamate Release In The Dentate Gyrus Of The Hippocampus Through The Stxbp5/Tomosyn-1 Gene, Seth R. Batten, Elena A. Matveeva, Sidney W. Whiteheart, Thomas C. Vanaman, Greg A. Gerhardt, John T. Slevin

Psychology Faculty Publications

Introduction: In kindling, repeated electrical stimulation of certain brain areas causes progressive and permanent intensification of epileptiform activity resulting in generalized seizures. We focused on the role(s) of glutamate and a negative regulator of glutamate release, STXBP5/tomosyn-1, in kindling.

Methods: Stimulating electrodes were implanted in the amygdala and progression to two successive Racine stage 5 seizures was measured in wild-type and STXBP5/tomosyn-1^−/− (Tom^−/−) animals. Glutamate release measurements were performed in distinct brain regions using a glutamate-selective microelectrode array (MEA).

Results: Naïve Tom^−/− mice had significant increases in KCl-evoked glutamate release compared to naïve wild type as …

Accurate Cytogenetic Biodosimetry Through Automated Dicentric Chromosome Curation And Metaphase Cell Selection, Jin Liu, Yanxin Li, Ruth Wilkins, Canadian Nuclear Laboratories, Joan H. Knoll, Peter Rogan

Biochemistry Publications

Accurate digital image analysis of abnormal microscopic structures relies on high quality images and on minimizing the rates of false positive (FP) and negative objects in images. Cytogenetic biodosimetry detects dicentric chromosomes (DCs) that arise from exposure to ionizing radiation, and determines radiation dose received based on DC frequency. Improvements in automated DC recognition increase the accuracy of dose estimates by reclassifying FP DCs as monocentric chromosomes or chromosome fragments. We also present image segmentation methods to rank high quality digital metaphase images and eliminate suboptimal metaphase cells. A set of chromosome morphology segmentation methods selectively filtered out FP DCs …

Clinical And Experimental Studies Of A Novel P525r Fus Mutation In Amyotrophic Lateral Sclerosis, Lisha Kuang, Marisa Kamelgarn, Alexandra Arenas, Jozsef Gal, Deborah Taylor, Weiming Gong, Martin Brown, Daret St. Clair, Edward J. Kasarskis, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Objective: To describe the clinical features of a novel fused in sarcoma (FUS) mutation in a young adult female amyotrophic lateral sclerosis (ALS) patient with rapid progression of weakness and to experimentally validate the consequences of the P525R mutation in cellular neuronal models.

Methods: We conducted sequencing of genomic DNA from the index patient and her family members. Immunocytochemistry was performed in various cellular models to determine whether the newly identified P525R mutant FUS protein accumulated in cytoplasmic inclusions. Clinical features of the index patient were compared with 19 other patients with ALS carrying the P525L mutation in the same …

Naturally-Derived Molecular Ensembles In Medicine, Materials Science And Evolutionary Biology: An Interdisciplinary Study, Silvio Panettieri

Dissertations, Theses, and Capstone Projects

The first chapter will introduce the work carried out in collaboration with the Govind laboratory at CCNY. Our quest was set forth to investigate the intimate relationship lying between chronic inflammation and tumor development. For at least the last fifteen years much research has been conducted on this topic; yet, the level of complexity arising from exceedingly interwoven biochemical pathways in mammals has resulted in slow advancements in this field. This is why we resorted to a simple yet powerful immunogenetic model organism, the fruit fly Drosophila melanogaster, in combination with the administration of the most common anti-inflammatory drug, …

Examination Of The Monoamine Oxidase A Gene Promoter On Motivation To Exercise And Levels Of Voluntary Physical Activity, Erin M. Kinney

Senior Theses

Purpose: The purpose of this study was to examine the genetic basis underlying voluntary exercise. Monoamine oxidase A (MAO-A) is an enzyme that acts on monoamine neurotransmitters, such as dopamine, to cause inactivation. There are several polymorphisms in the promoter region of the MAO-A gene, and these variations change transcriptional activity and the amount of MAO-A produced, leading to alterations in available dopamine levels. Interestingly, polymorphisms in MAO-A have been associated recently with physical activity level. This study sought to determine whether there is an association between motivation to exercise, levels of voluntary physical activity, and MAO-A gene polymorphisms.

Methods: …

Characterization Of Neuronal Specific Responses To Induced Misfolded Protein Stress In Caenorhabditis Elegans, Claire Gormley

Senior Honors Projects, 2010-2019

Abstract

Misfolded protein stress has been associated with many types of disease,

including neurodegenerative disorders like Alzheimer’s, Parkinson’s and Huntington’s

disease. When a cell accumulates misfolded proteins in the endoplasmic reticulum,

misfolded protein stress occurs and the unfolded protein response (UPR) is triggered to

induce mechanisms that will allow the cell to either survive or undergo cell death. The

nascent polypeptide associated complex (NAC) is a co-translational chaperone and α/β

heterodimer that manages protein folding and localization, and protects against misfolded

protein stress; changes in NAC function have been linked to both neurodegeneration and

cancer. In these studies, I depleted …

Epigenetic Modifications Of Human Placenta Associated With Preterm Birth, Drissa Toure

Theses & Dissertations

Preterm birth is a complex multifactorial process. Despite the well-known role of the placenta in supporting the fetal development and maternal-fetal tolerance, the placental epigenetic modifications and preterm birth (PTB) remains poorly understood and under investigated. Various maternal and environment factors can influence epigenetic programming during fetal development to affect the functioning and structures of organs, including the placenta, which can lead to adverse pregnancy outcomes, including PTB. The understanding of the placental epigenetic alterations and maternal determinants associated with PTB are apparently indispensable for the development of actual diagnosis and methods of prevention and treatment of premature labor. The …

Barriers To Expansion Of Supervision Networks At Genetic Counseling Training Programs, Jordan E. Berg

Dissertations and Theses (Open Access)

Job openings outpace new graduates due to exponential growth in genetic counseling, leading to a workforce shortage. Expanding training slots to meet this demand presumably is linked to the number of supervisors. Thus, there is a need to systematically review barriers to supervision. This study aimed to determine and compare barriers to expansion of supervision networks at genetic counseling training programs as perceived by current supervisors, non-supervisors, and Program Directors. Certified genetic counselors were recruited via National Society of Genetic Counselors e-blast with an invitation to complete an online survey; Program Directors were emailed personal letters of invitation. Twenty-three Program …

Attitudes To Ward And Uptake Of Prenatal Genetic Screening And Testing In Twin Pregnancies, Kathryn M. Reese

Dissertations and Theses (Open Access)

The rate of twinning is rising and is associated with delayed age at childbirth and increased infertility treatments. Since the introduction of non-invasive prenatal testing, interest in and uptake of genetic screening and testing in twin pregnancies has not been investigated. Therefore, this study aimed to describe the attitudes toward and uptake of current prenatal genetic screening and testing options in twin pregnancies. Forty-two women with twin gestations were recruited from UTHealth and Baylor College of Medicine sites between August 2016 and January 2017 for participation in a descriptive study consisting of a questionnaire (n=42) and semi-structured phone interview (n=15). …

The Utilization Of Prenatal Microarray: A Survey Of Current Genetic Counseling Practices And Barriers, Leslie N. Durham, Leslie Durham

Dissertations and Theses (Open Access)

Chromosomal microarray (CMA) assesses chromosome copy number variants (CNVs) missed by standard karyotyping. The American College of Obstetricians and Gynecologists (ACOG) recommends CMA for all patients with fetuses with an ultrasound anomaly and suggests that it be made available to all women undergoing invasive testing. In order to assess prenatal genetic counselors’ (GCs) practices regarding the utilization of CMA we conducted a survey of their current practices, attitudes, and perceived barriers. Of the 192 respondents, 183 (95%) have incorporated CMA into clinical practice with the majority (64%) believing that the benefits of CMA outweigh the harms. However, only half (52%) …

Undergraduate Student Perceptions And Awareness Of Genetic Counseling, Amanda Gerard

Dissertations and Theses (Open Access)

Genetic counseling (GC) is a rapidly expanding field, and the supply of certified genetic counselors is currently unable to keep up with job demand. Research is fairly limited regarding the awareness and perceptions potential genetic counseling program applicants have of the field and what factors most influence their interest in the field. This study aimed to examine some of these topics. The current study includes data collected from 1,389 undergraduate students in the sciences at 23 universities across the United States who were surveyed regarding information related to their awareness, perceptions, knowledge, and interest in GC. Data analysis was performed …

Attitudes Of Clinicians To Wards Cardiac Surgery And Trisomy 18, Meagan Kaulfus

Dissertations and Theses (Open Access)

Trisomy 18 is an autosomal trisomy characterized by minor to major birth defects, severe disabilities, and high rates of pre- and neonatal mortality. Interventions for these infants have traditionally been withheld with focus instead on palliative support. The issues and attitudes surrounding surgical treatment of congenital heart defects, which occur in approximately 90% of infants with trisomy 18, is of our study’s interest as recent literature has indicated that cardiac surgery is being performed and may lead to improved survival compared to palliative care. In this study, the attitudes of clinicians of multiple specialties towards cardiac surgery for infants with …

Differential Mrna Expression In Ectopic Germinal Centers Of Myasthenia Gravis Thymus, Manjistha Sengupta, Bi-Dar Wang, Norman H. Lee, Gary Cutter, Linda L. Kusner, Henry J. Kaminski

GW Research Days 2016 - 2020

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder resulting in weakness of voluntary muscles. It is caused by antibodies directed against proteins present at the post-synaptic surface of neuromuscular junction (NMJ). A characteristic pathology of patients with early onset MG is thymic hyperplasia with ectopic germinal centers (GC). However, mechanisms that trigger and maintain thymic hyperplasia are poorly characterized.

In order to determine the central mechanisms involved in the pathology, thymus samples from MG patients were assessed by histology and grouped based on appearance of GC compared to samples without them. We assessed the differential mRNA expression profiles between the …

Hla-B*57:01 Allele Prevalence In Hiv-Infected North American Subjects And The Impact Of Allele Testing On The Incidence Of Abacavir-Associated Hypersensitivity Reaction In Hla-B*57:01-Negative Subjects, Catherine Small, D Margolis, M Shaefer, L Ross

NYMC Faculty Publications

BACKGROUND: The presence of the HLA-B*57:01 allele in HIV-infected subjects is associated with a higher risk of abacavir-associated hypersensitivity reaction (ABC HSR). HLA-B*57:01 allele prevalence varies in different populations, but HLA-B*57:01 testing with immunological confirmation has had a negative predictive value for ABC HSR between 97 and 100%. METHODS: In the ASSURE study (EPZ113734), the HLA-B*57:01 prevalence in virologically suppressed, antiretroviral treatment-experienced, HIV-infected subjects from the United States, including Puerto Rico, was assessed. RESULTS: Three hundred eighty-five subjects were screened; 13 were HLA-B*57:01 positive and 372 were negative. Only HLA-B*57:01-negative, abacavir-naive subjects were eligible to enroll into the ASSURE trial. …

Sumo Regulates The Activity Of Smoothened And Costal-2 In Drosophila Hedgehog Signaling, Jie Zhang, Yajuan Liu, Kai Jiang, Jianhang Jia

Markey Cancer Center Faculty Publications

In Hedgehog (Hh) signaling, the GPCR-family protein Smoothened (Smo) acts as a signal transducer that is regulated by phosphorylation and ubiquitination, which ultimately change the cell surface accumulation of Smo. However, it is not clear whether Smo is regulated by other post-translational modifications, such as sumoylation. Here, we demonstrate that knockdown of the small ubiquitin-related modifier (SUMO) pathway components Ubc9 (a SUMO-conjugating enzyme E2), PIAS (a SUMO-protein ligase E3), and Smt3 (the SUMO isoform in Drosophila) by RNAi prevents Smo accumulation and alters Smo activity in the wing. We further show that Hh-induced-sumoylation stabilizes Smo, whereas desumoylation by Ulp1 …

Hypoxia Inducible Factor 1: A Urinary Biomarker Of Kidney Disease., S Movafagh, Dominic Raj, M Sanaei-Ardekani, D Bhatia, K Vo, M Mahmoudieh, R Rahman, E H Kim, Arthur F Harralson

Medicine Faculty Publications

Identifying noninvasive biomarkers of kidney disease is valuable for diagnostic and therapeutic purposes. Hypoxia inducible factor 1 (HIF-1) expression is known to be elevated in the kidneys in several renal disease pathologies. We hypothesized that the urinary HIF-1a mRNA level may be a suitable biomarker for expression of this protein in chronic kidney disease (CKD). We compared HIF-1a mRNA levels from urine pellets of CKD and healthy subjects. To ensure that urinary HIF-1a mRNA is of kidney origin, we examined colocalization of HIF-1a mRNA with two kidney specific markers in urine cells. We found that HIF-1a mRNA is readily quantifiable …

The Molecular Basis Of Talin2'S High Affinity Toward Β1-Integrin, Yaxia Yuan, Liqing Li, Yanyan Zhu, Lei Qi, Latifeh Azizi, Vesa P. Hytönen, Chang-Guo Zhan, Cai Huang

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Talin interacts with β-integrin tails and actin to control integrin activation, thus regulating focal adhesion dynamics and cell migration. There are two talin genes, Tln1 and Tln2, which encode talin1 and talin2, and it is generally believed that talin2 functions redundantly with talin1. However, we show here that talin2 has a higher affinity to β1-integrin tails than talin1. Mutation of talin2 S339 to leucine, which can cause Fifth Finger Camptodactyly, a human genetic disease, completely disrupted its binding to β–integrin tails. Also, substitution of talin1 C336 with Ser enhanced the affinity of talin1, whereas substitution of talin2 S339 with …