More than 7,000 rare Mendelian diseases have been reported, but less than half of all rare monogenic disorders has been discovered. In addition, the majority of mutations that are known to cause Mendelian disorders are located in protein-coding regions. Therefore, exome sequencing is an efficient strategy to selectively sequence the coding regions of the human genome to identify novel genes associated with rare genetic disorders. The "exome" represents all of the exons in the human genome, constituting about 1.5% of the human genome. Exome sequencing is carried out by targeted capture and intense parallel sequencing. After the first report of successful exome sequencing for the identification of causal genes and mutations in Freeman Sheldon syndrome, exome sequencing has become a standard approach to identify genes in rare Mendelian disorders. Exome sequencing is also used to search the causal genes and variants in complex diseases. The successful use of exome sequencing in Mendelian disorders and complex diseases will facilitate the development of personalized genomic medicine.
Clinical Coding ; Exome ; Exons ; Genome, Human ; Humans

PURPOSE: Breast volume is one of the crucial measurements in preoperative planning and postoperative evaluation of the results in mammoplasty. There are several methods suggested by different authors, but there is still no commonly accepted standard methods for measuring breast volume. To help the surgeons to base their estimation on an objective evaluation, we developed a simple method using Polyethylene bag and plaster molding. METHODS: After Polyethylene bags were put in suitable size on both breasts of the patient in upright position, silk plaster was molded on the surface evenly. Then molds can be obtained after marking boundaries of breasts with a pen. Breast volume measurement can be done by filling water in the molds and measuring it. Moreover, postoperative design for natural skin brassier was possible using the molds. RESULTS: This method was applied to 2 patients for reduction mammoplasty and the breast volume measurement was simple, hygienic and accurate, done within 10 minutes. CONCLUSION: This method using Polyethylene bag and plaster molding has several advantages. 1.It is comparatively accurate regardless of the size and shape of patient's breasts in upright position. 2.Measurement time is short and inconvenience and shame of patients can be reduced by making molds after putting on Polyethylene bags. 3.It is relatively economical and uses easily available hygienic materials . 4.The postoperative shape and volume of breasts can be predicted by using molds preoperatively.
Breast* ; Female ; Fungi* ; Humans ; Mammaplasty ; Polyethylene* ; Shame ; Silk ; Skin ; Water

PURPOSE: Wilson disease is an autosomal recessive disorder which causes excessive copper accumulation in the hepatic region. So far, ATP7B gene is the only disease-causing gene of Wilson disease known to date. However, ATP7B mutations have not been found in ~15% of the patients. This study was performed to identify any causative gene in Wilson disease patients without an ATP7B mutation in either allele. MATERIALS AND METHODS: The sequence of the coding regions and exon-intron boundaries of the five ATP7B-interacting genes, ATOX1, COMMD1, GLRX, DCTN4, and ZBTB16, were analyzed in the 12 patients with Wilson disease. RESULTS: Three nonsynonymous variants including c.1084A>G (p.Thr362Ala) in the exon 12 of the DCTN4 gene were identified in the patients examined. Among these, only p.Thr362Ala was predicted as possibly damaging protein function by in silico analysis. Examination of allele frequency of c.1084A>G (p.Thr362Ala) variant in the 176 patients with Wilson disease and in the 414 normal subjects revealed that the variant was more prevalent in the Wilson disease patients (odds ratio [OR]=3.14, 95% confidence interval=1.36-7.22, P=0.0094). CONCLUSION: Our result suggests that c.1084A>G (p.Thr362Ala) in the ATP7B-interacting DCTN4 gene may be associated with the pathogenesis of Wilson disease.
Clinical Coding ; Computer Simulation ; Copper ; Exons ; Gene Frequency ; Hepatolenticular Degeneration ; Humans

Today most developed countries provide modern medical care for most of the population. The rural area is the more neglected area in the medical and health field. In public health, the philosophy is that medical care for in maintenance of health is a basic right of man; it should not be discriminated against racial, environmental or financial situations. The deficiency of the medical care system, cultural bias, economic development, and ignorance of the residents about health care brought about the shortage of medical personnel and facilities on the rural areas. Moreover, medical students and physicians have been taught less about rural health care than about urban health care. Medical care, therefore, is insufficient in terms of health care personnel and facilities in rural areas. Under such a situation, there is growing concern about the health problems among the rural population. the findings presented in this report are useful measures of the major health problems an even more important, as a guide to planning for improves medical care systems. It is hoped that findings from this study will be useful to those responsible for improving the delivery of health service for the rural population. Objectives: -to determine the health status of the residents in the rural area. -to assess the rural population's needs in terms of health and medial care. -to make recommendations concerning improvement in the delivery of health and medical care for the rural population. Procedures: For the sampling design, the ideal would be to sample according to the proportion of the composition age-groups. As the health problems would be different by group , the sample was divided into 10 different age-groups. If the sample were allocated by proportion of composition of each age group, some age groups would be too small to estimate the health problem. The sample size of each age-group population was 100 people/age-groups. Personal interviews were conducted by specially trained medical students. The interviews dealt at length with current health status, medical care problems, utilization of medical services, medical cost paid for medical care and attitudes toward health. In addition, more information was gained from the public health field, including environmental sanitation, maternal and child health, family planning, tuberculosis control, and dental health. The sample: Sample size was one fourth of total population: 1,438. The aged 10-14 years showed the largest number of 254 and the aged under one year was the smallest number of 81. Participation in examination. Examination sessions usually were held in the morning every Tuesday, Wednesday, and Thursday for 3 hours at each session at the Namchun Health station. In general, the rate of participation in medical examination was low especially in ages between 10-19 years old. The highest rate of participation among are groups was the under one year age-group by 100 percent. The lowest use rate as low as 3% of those in the age-groups 10-19 years who are attending junior and senior hgh school in Taegu city so the time was not convenient for them to receive examinations. Among the over 20 years old group, the rate of participation of female was higher than that of males. The results are as follows: A. Public health problems. Population: The number of pre-school age group who required child health was 724, among them infants numbered 96. Number of eligible women aged 15-44 years was 1,279, and women with husband who need maternal health numbered 700. The age-group of 65 years of older was 201 needed more health care and 65 of them had disabilities (table 2). Environmental sanitation: Seventy-nine percent of the residents relied upon well water as a primary source of drinking. More than 90% of latrines were unhygienic, in structure design and sanitation (Table 15). Maternal and child health: Maternal health. Average number of pregnancies of eligible women was 4 times. There was almost no pre-and post-natal care. Pregnancy wastage. Still births was 33 per 1,000 live births. Spontaneous abortion was 156 per 1,000 live births. Induced abortion was 137 per 1,000 live births. Delivery Condition. More than 90 percent of deliveries were conducted at home. Attendants at last delivery were laymen by 76% and delivery without attendants was 14%. The rate of difficult delivery counted for 3%. Maternal death rate estimate about 35 per 10,000 live births. Child health. Consultation rate for child health was almost non existent. In general, vaccination rate of children was low; vaccination rates for children but the rate of the complete three injections were as low as 5 and 3% respectively. The number of dead children was 280 per 1,000 living children. Infants death rate was 45 per 1,000 live births (Table 16). Family planning: Approval rate of married women for family planning was as high as 86%. The rate of experiences of contraception in the past was 51%. The current rate of contraception was 37%. Willingness to use contraception in the future was as high as 86% (Table 17). Tuberculosis control: Number of registration patients at the health center currently was 25. The number indicates one eight of estimate number of tuberculosis in the area. Number of discharged cases in the pat accounted for 79 which showed 50% of active cases when discharged time. Rate of complete treatment among reasons of discharge on the past as low as 28%. There needs to be a follow up observation of the discharged cases (Table 18). Dental Problems: More than 50% of the total population have lest one or more dental problems. (Table 19) B. Medical care Problems. Incidence rate: 1. In one month. Incidence rate of medical care problems during one month was 19.6% percent. Among these health problems which required rest at home were 11.8 percent. The estimated number of patients in the total population is 1,206. The health problems reported most frequently in interviews during one month are: GI trouble, respiratory disease, neuralgia, skin disease, and communicable disease-n the order. The rate of health problems by age groups was highest in the 1-4 age group and in the 60 years of over age group, the lowest rate was the 10-14 year age group. In general, 0-29 year age group except the 1-4 year age group was low incidence rate. After 30 years old th rate of health problems increases gradually with aging. Eighty-three percent of health problems that occurred during one month were solved by primary medical care procedures. Seventeen percent of health problems needed secondary care. Days rested at those because of illness during one month were 1.7days per interviewee and 8days per patient and it accounts for 2,161 days for the total productive population in the area. (Table 20) 2. In a year. The incidence rate of medical care problems during a year was 7.8%, among them health problems which required rest at those was 37 percent. Estimated number of patients in the total population during a year was 4,600. The health problems that occurred most frequently among the interviewees during a year were: Cold (30%), GI trouble (18), respiratory disease (11), anemia (10) ,diarrhea (10), neuralgia (10), parasite disease (9), ENT (7), skin (7), headache (7), trauma (4), communicable disease (3), and circulatory disease (3)-in that order. The rate of health problems by age groups was highest in the infants group, thereafter the rate decreased gradually until the age group which showed the lowest, and then the rate increased gradually with aging. Eighty-seven percent of health problems during a year were 16 days per interviewee and 4 days per patient and it accounted for 57,335 days lost among productive age group in the area (Table 21). Among those given medical examination, the conditions observed most frequency were respiratory disease, GI trouble, parasite disease, neuralgia, skin disease, trauma, tuberculosis, anemia, chronic obstructive lung disease, eye disorders-in that order (Table 22). The main health problems required secondary medical care are as follows:(previous page). Utilization of medical care (treatment) by various medical for all health problems during one month was 73 percent. The rate of receiving of medical care of those who have health problems which required rest at home was 82% while the rate of those who have health problems which did not required rest was 61percent (Table 23). The rate of receiving of medical care for all health problems during a year was 67 percent. The rate of receiving of medical care of those who have health problems which required rest at home was 82 percent while the rate of those who have health problems which did not required rest was as low as 53 percent (Table 24). Types of medical facilitated used were as follows: Hospital and clinics: 32-35%. Herb clinics: 9-10%. Drugstore: 53-58%. Hospitalization. Rate of hospitalization was 1.7% and the estimate number of hospitalization among the total population during a year will be 107 persons (Table 25). Medical cost: Average medical cost per person during one month and a year were 171 and 2,800 won respectively. Average medical cost per patient during one month and a year were 1,1109 and 3,740 won respectively. Average cost per household during a year was 15,800 won (Table 26, 27).Solution measures for health and medical care problems in rural area: A. Health problems which could be solved by paramedical workers such as nurses, midwives and aid nurses etc. are as follows: 1. Improvement of environmental sanitation. 2. MCH except medical care problems. 3. Family planning except surgical intervention. 4. Tuberculosis control except diagnosis and prescription. 5. Dental care except operational intervention. 6. Health education for residents for improvement of utilization of medical facilities and early diagnosis etc. b. Medical care problems. 1. Eighty-five percent of health problems could be solved by primary care procedures by general practitioners. 2. Fifteen percent of health problems need secondary medical procedures by a specialist. C. Medical cost. Considering the economic situation in rural area the amount of 2,062 won per residents during a year will be burdensome, so financial assistance is need government to solve health and medical care problems for rural people.
Abortion, Induced ; Abortion, Spontaneous ; Adult ; Aging ; Anemia ; Bias (Epidemiology) ; Child ; Child Health ; Communicable Diseases ; Contraception ; Daegu ; Delivery of Health Care ; Dental Care ; Developed Countries ; Diagnosis ; Diarrhea ; Drinking ; Early Diagnosis ; Economic Development ; Family Characteristics ; Family Planning Services ; Female ; Follow-Up Studies ; General Practitioners ; Headache ; Health Education ; Health Services ; Hope ; Hospitalization ; Humans ; Incidence ; Infant ; Korea* ; Live Birth ; Male ; Maternal Death ; Maternal Health ; Midwifery ; Mortality ; Neuralgia ; Parasites ; Parturition ; Philosophy ; Pregnancy ; Prescriptions ; Primary Health Care ; Public Health ; Pulmonary Disease, Chronic Obstructive ; Rural Health ; Rural Population ; Sample Size ; Sanitation ; Secondary Care ; Skin ; Skin Diseases ; Specialization ; Spouses ; Students, Medical ; Toilet Facilities ; Tuberculosis ; Urban Health ; Vaccination ; Young Adult

The role of Mac-1 as a receptor for Bordetella bronchiseptica infection of alveolar macrophages (AMphi) was examined using 6 strains (2 ATCC and 4 pathogenic field isolates) to assess B. bronchiseptica binding, uptake and replication in primary porcine AMphi. All B. bronchiseptica strains were rapidly killed by porcine serum in a dose- and time-dependent manner. However, heat-inactivated porcine serum (HIS) did not demonstrate any bacterial-killing activity, suggesting that complement may have a direct killing activity. All field isolates were more resistant to direct complement-mediated B. bronchiseptica killing. The uptake of B. bronchiseptica into AMphi was inhibited approximately 50% by antiMac-1 monoclonal antibodies in the medium. However, B. bronchiseptica phagocytosed in the presence of serum or HIS was not altered by anti-Mac-1 antibodies although more bacteria were internalized by addition of serum or HIS. These data suggest that Mac-1 is a target for direct uptake of B. bronchiseptica via opsoninindependent binding. The phagocytosed B. bronchiseptica, either via direct or serum-mediated binding, were efficiently killed by AMphi within 10 hr postinfection. This demonstrates that Mac-1-mediated B. bronchiseptica uptake is a bacterial killing pathway not leading to productive infections in AMphi.
Animals ; Antibodies, Bacterial/blood/immunology ; Bordetella bronchiseptica/*immunology ; Macrophage-1 Antigen/*immunology ; Macrophages, Alveolar/*immunology ; Phagocytosis ; Protein Binding ; Swine/*immunology/*microbiology

Monomelic amyotrophy (MA), also known as Hirayama disease, occurs mainly in young men and manifests as weakness and wasting of the muscles of the distal upper limbs. Here, we sought to identify a genetic basis for MA. Given the predominance of MA in males, we focused on candidate neurological disease genes located on the X chromosome, selecting two X-linked candidate genes, androgen receptor (AR) and ubiquitin-like modifier activating enzyme 1 (UBA1). Screening for genetic variants using patients' genomic DNA revealed three known genetic variants in the coding region of the AR gene: one nonsynonymous single-nucleotide polymorphism (SNP; rs78686797) encoding Leu57Gln, and two variants of polymorphic trinucleotide repeat segments that encode polyglutamine (CAG repeat; rs5902610) and polyglycine (GGC repeat; rs3138869) tracts. Notably, the Leu57Gln polymorphism was found in two patients with MA from 24 MA patients, whereas no variants were found in 142 healthy male controls. However, the numbers of CAG and GGC repeats in the AR gene were within the normal range. These data suggest that the Leu57Gln polymorphism encoded by the X-linked AR gene may contribute to the development of MA.
Case-Control Studies ; Clinical Coding ; DNA ; Genes, X-Linked ; Humans ; Male ; Mass Screening ; Muscles ; Peptides ; Receptors, Androgen ; Reference Values ; Spinal Muscular Atrophies of Childhood ; Trinucleotide Repeats ; Upper Extremity ; X Chromosome

OBJECTIVES: The molecular mechanisms underlying attention-deficit hyperactivity disorder (ADHD) remain unclear. Therefore, this study aimed to identify the genetic susceptibility loci for ADHD in Korean children with ADHD. We performed a case-control and a family-based genome-wide association study (GWAS), as well as genome-wide quantitative trait locus (QTL) analyses, for two symptom traits. METHODS: A total of 135 subjects (71 cases and 64 controls), for the case-control analysis, and 54 subjects (27 probands and 27 unaffected siblings), for the family-based analysis, were included. RESULTS: The genome-wide QTL analysis identified four single nucleotide polymorphisms (SNPs) (rs7684645 near APELA, rs12538843 near YAE1D1 and POU6F2, rs11074258 near MCTP2, and rs34396552 near CIDEA) that were significantly associated with the number of inattention symptoms in ADHD. These SNPs showed possible association with ADHD in the family-based GWAS, and with hyperactivity-impulsivity in genome-wide QTL analyses. Moreover, association signals in the family-based QTL analysis for the number of inattention symptoms were clustered near genes IL10, IL19, SCL5A9, and SKINTL. CONCLUSION: We have identified four QTLs with genome-wide significance and several promising candidates that could potentially be associated with ADHD (CXCR4, UPF1, SETD5, NALCN-AS1, ERC1, SOX2-OT, FGFR2, ANO4, and TBL1XR1). Further replication studies with larger sample sizes are needed.
Adolescent* ; Case-Control Studies ; Child ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Humans ; Interleukin-10 ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Sample Size

Obesity provokes many serious human diseases, including various cardiovascular diseases and diabetes. Body mass index (BMI) is a highly heritable trait that is broadly used to diagnose obesity. To identify genetic loci associated with obesity in Asians, we conducted a genome-wide association study (GWAS) of a population of Korean adults (n=6,742, age 40~60 years) and detected six BMI risk loci (TNR, FAM124B, RGS12, NFE2L3, MC4R and FTO) having p<1x10(-5). However, in the replication study, only melanocortin 4 receptor gene (MC4R) (rs9946888, p=4.58x10(-7)) was replicated with marginal significance (p<0.05) in the second cohort (n=5,102, age 40~60 years). This study indicates that each locus associated with BMI has very weak genetic effect.
Adult ; Asian Continental Ancestry Group ; Body Mass Index ; Cardiovascular Diseases ; Cohort Studies ; Genetic Loci ; Genome-Wide Association Study ; Humans ; Obesity ; Receptor, Melanocortin, Type 4

BACKGROUND AND PURPOSE: Variant alleles of CYP2C9 and VKORC1 account for differences in anticoagulation response. We sought to establish a warfarin dosing formula for individualized target International Normalization Ratio of Prothrombin Times (INRs) using data from single nucleotide polymorphisms (SNPs) in VKORC1 and CYP2C9 in Korean patients. METHODS: Ischemic stroke patients displaying stable target INR for at least 3 months before enrollment were analyzed. Warfarin and vitamin K levels were measured to adjust for confounders. Phenotypes were defined using the 'warfarin response index' (WRI) defined as INR divided by the daily maintenance warfarin dose. We tested SNPs in CYP2C9 (3 sites: 430C>T (rs1799853), 1075A>C (rs1057910), 1076T>C) and VKORC1 (14 sites: 381C>T, 861C>A (rs17880887), 2653G>C, 3673A>G, 5496G>T, 5808T>G (r17882154), 6009C>T, 6484T>C (rs9934438), 6853C>T (rs17886369), 7566T>C, 8767G>C, 8814T>C, 9041G>A (rs17880624), and 9071G>T) using a standard sequencing method. Multivariate linear regression analysis was applied to establish the formula for warfarin dosage. RESULTS: All 204 patients had excellent drug compliance. The mean INR was 2.22 (+0.56) and mean daily maintenance dose of warfarin was 3.92 mg (+1.54). Patients with low WRI were younger (P<0.001) with high body mass index (P=0.003), high prevalence of wild-type CYP2C9 polymorphism (1075A>C, P<0.001), and six heterozygote SNPs in VRORC1 (P<0.001), which were tightly interlinked (381T>C, 3673G>A, 6484T>C, 6853C>G. 7566C>T, 9041G>A) (r2=1). Based on these data, a warfarin dosing formula was established. CONCLUSIONS: WRI is influenced by age, body mass index and SNPs in VKORC1 and CYP2C9 in Korean stroke patients. The obtained warfarin dosing formula may be clinically applicable.
Alleles ; Body Mass Index ; Compliance ; Genotype ; Heterozygote ; Humans ; International Normalized Ratio ; Linear Models ; Phenotype ; Polymorphism, Single Nucleotide ; Prevalence ; Prothrombin Time ; Stroke ; Vitamin K ; Warfarin