Microsatellite polymorphism at the D9S12 locus

Human Genetics, 1993

The locus for Tyrosinase-Positive Oculocutaneous Albinism (ty-pos OCA) has not yet been localised. The search for the ty-pos OCA locus has included a search for linkage to candidate pigment loci and a candidate chromosomal region, as well as a random search using highly polymorphic markers in 42 families, including 271 individuals of whom 79 are affected. The lod scores for the tyrosinase (TYR) locus (11q14–q21), homologous to the albino locus, c, in the mouse and the CAS2/TRP1 locus (9p22-pter), homologous to the brown locus, b, in the mouse were -5.89 and -7.22, respectively, at a recombination fraction of θ=0.01, thus excluding them from being the ty-pos OCA locus. In the candidate chromosomal region, 11p, four loci (probes) were tested, SAA (pSAA82), CALC (pHC36), HBB (Gamma-globin haplotype) and an AC repeat polymorphism at the Wilm's Tumour locus (WT1). A portion of 11p was excluded with the following lod scores: pSAA82 lod=-2.05 at θ=0.10; pHC36 lod=-3.87 at θ=0.05; gamma-globin haplotype lod=-2.80 at θ=0.10; and WT1 lod=-2.34 at θ=0.10. Thirty-three polymorphic markers randomly distributed on 13 different chromosomes were all excluded from close linkage to ty-pos OCA.

International journal of ophthalmology, 2016

The American Journal of Human Genetics, 1997

Oculocutaneous albinism (OCA) is the most common autosomal recessive disorder among southern African Blacks. There are three forms that account for almost all OCA types in this region. Tyrosinase-positive OCA (OCA2), which is the most common, affects -1/3,900 newborns and has a carrier frequency of -1/33. It is caused by mutations in the P gene on chromosome 15. Brown OCA (BOCA) and rufous OCA (ROCA) account for the majority of the remaining phenotypes. The prevalence of BOCA is unknown, but for ROCA it is A1/8,500. Linkage analysis performed on nine ROCA families showed that ROCA was linked to an intragenic marker at the TYRP1 locus (maximum LOD score = 3.80 at 0 = .00). Mutation analysis of 19 unrelated ROCA individuals revealed a nonsense mutation at codon 166 (S166X) in 17 (45%) of 38 ROCA chromosomes, and a second mutation (368delA) was found in an additional 19 (50%) of 38 chromosomes; mutations were not identified in the remaining 2 ROCA chromosomes. In one family, two siblings with a phenotypically unclassified form of albinism were found to be compound heterozygotes for mutations (S166X/ 368delA) at the TYRP1 locus and were heterozygous for a common 2.7-kb deletion in the P gene. These findings have highlighted the influence of genetic background on phenotype, in which the genotype at one locus can be influenced by the genotype at a second locus, leading to a modified phenotype. ROCA, which in southern African Blacks is caused by mutations in the TYRP1 gene, therefore should be referred to as "OCA3," since this is the third locus that has been shown to cause an OCA phenotype in humans.

Molecular Genetics and Metabolism, 1998

British Journal of Dermatology, 2010

Background Oculocutaneous albinism (OCA) refers to a group of inherited disorders where the patients have little or no pigment in the eyes, skin and hair. Mutations in genes regulating multi-step melanin biosynthesis are the basis of four 'classical' OCA types with overlapping clinical features. There are a few reports on defects in TYR and a single report on SLC45A2 in Indians affected with OCA but no report on OCA2 (a major locus related to the disease) and TYRP1. Objectives To assess and describe a comprehensive picture of the molecular genetic basis of OCA among Indians with no apparent mutations in TYR. Methods Twenty-four affected pedigrees from 14 different ethnicities were analysed for mutations in OCA2, TYRP1, SLC45A2 and SLC24A5 using the polymerase chain reaction-sequencing approach. Results Two splice-site and four missense mutations were detected in OCA2 in seven unrelated pedigrees, including four novel mutations. Haplotype analysis revealed a founder mutation (Ala787Thr) in two unrelated families of the same ethnicity. A patient homozygous for a novel SLC45A2 mutation also harboured a novel OCA2 defect. No mutation was detected in TYRP1 or SLC24A5. Conclusions Our results suggest that an OCA2 gene defect is the second most prevalent type of OCA in India after TYR. The presence of homozygous mutations in the affected pedigrees underscores the lack of intermixing between the affected ethnicities. Direct detection of the genetic lesions prevalent in specific ethnic groups could be used for carrier detection and genetic counselling to contain the disease.

Nucleic Acids Research, 1991

Acta Medica Philippina, 2009

Philippines Manila in 1999, houses the Cytogenetics Laboratory that services many hospitals throughout the country through processing of peripheral blood, cord blood, bone marrow and skin/tissue samples for cytogenetic analysis. Bone marrow, cord blood and skin/tissues account for 14.9%, 8.5% and 1.8% of samples analyzed, respectively, and the remainder are peripheral blood (74.8%). This paper presents the results of a retrospective review of the chromosomal analysis done on peripheral blood samples from 1991 to 2007. Of the 10655 samples submitted, 8391 were samples from patients and 2264 were research samples on cytogenetic effects of environmental toxins, (i.e. pesticides, etc.) on high risk populations. Of the 8391 patient samples analyzed, 73.0% were from hospitals in Luzon, 4.0% from Visayas, and 0.9% from Mindanao. Samples from private health practitioners' clinics from different parts of the country accounted for 11.7% of the samples received. There was no information given on source of sample in 10.3%. The top 3 reasons for referral for cytogenetic studies are confirmation of a chromosomal diagnosis, cytogenetic effects of environmental toxins (i.e. pesticides), and recurrent miscarriages/ poor obstetric history. Numerical chromosome abnormalities (86.6%) were more common than structural abnormalities (13.39%). Among the numerical abnormalities, 90.2% were autosomal, and Trisomy 21 is the most common type of aneuploidy seen. For sex chromosome abnormalities, the classic form of Turner was most prevalent. Deletions, additions, and translocations were the most predominantly ascertained structural abnormalities of the chromosomes in this review. This paper aims to review the abnormal results of the chromosomal analysis done on peripheral blood samples of patients processed by the Cytogenetics Laboratory of the Institute of Human Genetics from 1991 to 2007. Data of research samples will not be included in this paper.

The American Journal of Human Genetics, 1997

Inter-and Intrachromosomal Rearrangements Are priate informed consent, from the patient, both parents, and paternal grandparents. DNA was isolated by use of Both Involved in the Origin of 15q11-q13 Deletions in Prader-Willi Syndrome a QIAamp blood kit (Qiagen). We employed markers D15S541 and D15S542, both mapping to YAC To the Editor: A124A3, proximal to the deletion region, and markers Prader-Willi syndrome (PWS) is due to an interstitial de D15S165 and D15S1048, both mapping distal to the novo deletion at 15q11-q13 in Ç70% of cases. The common deletion region (Hudson et al. 1995). In addideletion spans a region of Ç4 Mb and invariably intion, marker ATC3C11, mapping õ1 Mb from the disvolves the paternally derived homologue (Robinson et tal deletion breakpoint (S. L. Christian and D. H. Ledal. 1991). For most patients the distal breakpoint apbetter, unpublished data), was used. PCR assays were pears to be located within a single YAC (Kuwano et al. performed as described elsewhere (Christian et al. 1995; 1992), whereas two consistent breakpoint hot spots Hudson et al. 1995). The results of the microsatellite have been identified on the proximal side; one (class I) analysis are shown in table 1, and examples of the analylies in the region between the centromere and D15S541/ sis performed on two independent families are shown D15S542, and the other (class II) lies between in figure 1. D15S541/D15S542 and D15S543, with each account-Three patients were deleted for the D15S541/D15S542 ing for approximately half of the deletions (Christian markers, thus being classified as class I-deletion patients. et al. 1995). This finding was consistent with the known frequency The relatively high frequency of deletions, significant of the class I breakpoints among PWS patients. The lack clustering of the breakpoints in PWS deletion patients, of a proximal marker on the deleted allele in these paand the finding of a similar location for the breakpoints tients precluded assessment of the haplotype for the rein small inv dup(15) has led to the hypothesis that small gion comprising the deletion. Of the seven class II paregions in proximal 15q may contain sequences leading tients, five demonstrated a paternal recombination event to instability (Knoll et al. 1993; Huang et al. 1997). between the markers flanking the common deletion re-Recently, preliminary data for a low-copy repeat associgion. The genetic distance between marker D15S541 and ated with a novel evolutionarily conserved gene family marker D15S165 has been estimated as 17.2 cM in males spanning the proximal and distal breakpoint regions has (Robinson and Lalande 1995). Marker D15S1048 maps been reported (Ji et al. 1996). 2 cM proximal to D15S165 (Hudson et al. 1995). ThereIn order to analyze the mechanism underlying delefore, when the genetic distance between D15S541 and tions in PWS, we genotyped 10 three-generation families D15S165 in male meiosis is taken into account, the idenof PWS-deletion patients, using microsatellite markers tification, in five of seven cases, of a different grandparenflanking the common deletion region. Each patient was tal origin for the alleles flanking the deletion is signifiknown to be deleted for the interval from D15S11 to cantly different from the expected frequency (x 2 GABRB3, by FISH and/or other molecular techniques. Å 12.438, P Å .0004). This finding is highly suggestive of an unequal crossover occurring in the paternal meio-Peripheral blood samples were obtained, with appro

American Journal of Hematology, 2000

The majority of the chromosomes with the ␤ S gene have one of the five common haplotypes, designated as Benin, Bantu, Senegal, Cameroon, and Arab-Indian haplotypes. However, in every large series of sickle cell patients, 5-10% of the chromosomes have less common haplotypes, usually referred to as "atypical" haplotypes. In order to explore the genetic mechanisms that could generate these atypical haplotypes, we extended our analysis to other rarely studied polymorphic markers of the ␤ S -gene cluster, in a total of 40 chromosomes with uncommon haplotypes from Brazil and Cameroon. The following polymorphisms were examined: seven restriction site polymorphisms of the ␥␦␤cluster, the pre-G ␥ framework sequence including the 6-bp deletion/insertion pattern, HS-2 LCR (AT)xR(AT)y and pre-␤ (AT)xTy repeat motifs, the GC/TT polymorphism at −1105-1106 of G ␥-globin gene, the C/T polymorphism at −551 of the ␤-globin gene, and the intragenic ␤-globin gene framework. Among the Brazilian subjects, the most common atypical structure (7/16) was a Bantu 3-subhaplotype associated with different 5sequences, while in two chromosomes a Benin 3-subhaplotype was associated with two different 5-subhaplotypes. A hybrid Benin/Bantu configuration was also observed. In three chromosomes, the atypical haplotype differed from the typical one by the change of a single restriction site. In 2/134 chromosomes identified as having a typical Bantu RFLPhaplotype, a discrepant LCR repeat sequence was observed, probably owing to a crossover 5 to the -gene. Among 80 ␤ S chromosomes from Cameroon, 22 were associated with an atypical haplotype. The most common structure was represented by a Benin haplotype (from the LCR to the ␤-gene) with a non-Benin segment 3 to the ␤-globin gene. In two cases a Bantu LCR was associated with a Benin haplotype and a non-Benin segment 3 to the ␤-globin gene. In three other cases, a more complex structure was observed that can be considered as a hybrid of Benin, Bantu, Senegal, or other chromosomes was observed. These data suggest that the atypical ␤ S haplotypes are not uncommon in America and in Africa. These haplotypes are probably generated by a variety of genetic mechanisms including (a) isolated nucleotide changes in one of the polymorphic restriction sites, (b) simple and double crossovers between two typical ␤ S haplotypes or much more frequently between a typical ␤ S haplotype and a different ␤ Aassociated haplotype that was present in the population, and (c) gene conversions. Am.